Alkaloids from Plants with Antimalarial Activity: A Review of Recent Studies
Identifieur interne : 000947 ( Pmc/Corpus ); précédent : 000946; suivant : 000948Alkaloids from Plants with Antimalarial Activity: A Review of Recent Studies
Auteurs : Philip F. UzorSource :
- Evidence-based Complementary and Alternative Medicine : eCAM [ 1741-427X ] ; 2020.
Abstract
Malaria is one of the major health problems in developing countries. The disease kills a large number of people every year and also affects financial status of many countries. Resistance of the plasmodium parasite, the causative agent, to the existing drugs, including chloroquine, mefloquine, and artemisinin based combination therapy (ACT), is a serious global issue in malaria treatment and control. This warrants an urgent quest for novel compounds, particularly from natural sources such as medicinal plants. Alkaloids have over the years been recognized as important phytoconstituents with interesting biological properties. In fact, the first successful antimalarial drug was quinine, an alkaloid, which was extracted from Cinchona tree. In the present review work, the alkaloids isolated and reported recently (2013 till 2019) to possess antimalarial activity are presented. Several classes of alkaloids, including terpenoidal, indole, bisindole, quinolone, and isoquinoline alkaloids, were identified with a promising antimalarial activity. It is hoped that the reports of the review work will spur further research into the structural modification and/or development of the interesting compounds as novel antimalarial drugs.
Url:
DOI: 10.1155/2020/8749083
PubMed: 32104196
PubMed Central: 7037883
Links to Exploration step
PMC:7037883Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Alkaloids from Plants with Antimalarial Activity: A Review of Recent Studies</title><author><name sortKey="Uzor, Philip F" sort="Uzor, Philip F" uniqKey="Uzor P" first="Philip F." last="Uzor">Philip F. Uzor</name><affiliation><nlm:aff id="I1">Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, 410001 Nsukka, Enugu State, Nigeria</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32104196</idno><idno type="pmc">7037883</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037883</idno><idno type="RBID">PMC:7037883</idno><idno type="doi">10.1155/2020/8749083</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000947</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000947</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Alkaloids from Plants with Antimalarial Activity: A Review of Recent Studies</title><author><name sortKey="Uzor, Philip F" sort="Uzor, Philip F" uniqKey="Uzor P" first="Philip F." last="Uzor">Philip F. Uzor</name><affiliation><nlm:aff id="I1">Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, 410001 Nsukka, Enugu State, Nigeria</nlm:aff></affiliation></author></analytic><series><title level="j">Evidence-based Complementary and Alternative Medicine : eCAM</title><idno type="ISSN">1741-427X</idno><idno type="eISSN">1741-4288</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Malaria is one of the major health problems in developing countries. The disease kills a large number of people every year and also affects financial status of many countries. Resistance of the plasmodium parasite, the causative agent, to the existing drugs, including chloroquine, mefloquine, and artemisinin based combination therapy (ACT), is a serious global issue in malaria treatment and control. This warrants an urgent quest for novel compounds, particularly from natural sources such as medicinal plants. Alkaloids have over the years been recognized as important phytoconstituents with interesting biological properties. In fact, the first successful antimalarial drug was quinine, an alkaloid, which was extracted from Cinchona tree. In the present review work, the alkaloids isolated and reported recently (2013 till 2019) to possess antimalarial activity are presented. Several classes of alkaloids, including terpenoidal, indole, bisindole, quinolone, and isoquinoline alkaloids, were identified with a promising antimalarial activity. It is hoped that the reports of the review work will spur further research into the structural modification and/or development of the interesting compounds as novel antimalarial drugs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ashok, P" uniqKey="Ashok P">P. Ashok</name></author><author><name sortKey="Ganguly, S" uniqKey="Ganguly S">S. Ganguly</name></author><author><name sortKey="Murugesan, S" uniqKey="Murugesan S">S. Murugesan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaur, K" uniqKey="Kaur K">K. Kaur</name></author><author><name sortKey="Jain, M" uniqKey="Jain M">M. Jain</name></author><author><name sortKey="Khan, S I" uniqKey="Khan S">S. I. Khan</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Schlitzer, M" uniqKey="Schlitzer M">M. Schlitzer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wiesner, J" uniqKey="Wiesner J">J. Wiesner</name></author><author><name sortKey="Ortmann, R" uniqKey="Ortmann R">R. Ortmann</name></author><author><name sortKey="Jomaa, H" uniqKey="Jomaa H">H. Jomaa</name></author><author><name sortKey="Schlitzer, M" uniqKey="Schlitzer M">M. Schlitzer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Onori, E" uniqKey="Onori E">E. Onori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kain, K C" uniqKey="Kain K">K. C. Kain</name></author><author><name sortKey="Shanks, G D" uniqKey="Shanks G">G. D. Shanks</name></author><author><name sortKey="Keystone, J S" uniqKey="Keystone J">J. S. Keystone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mugittu, K" uniqKey="Mugittu K">K. Mugittu</name></author><author><name sortKey="Genton, B" uniqKey="Genton B">B. Genton</name></author><author><name sortKey="Mshinda, H" uniqKey="Mshinda H">H. Mshinda</name></author><author><name sortKey="Beck, H P" uniqKey="Beck H">H. P. Beck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anthony, M P" uniqKey="Anthony M">M. P. Anthony</name></author><author><name sortKey="Burrows, J N" uniqKey="Burrows J">J. N. Burrows</name></author><author><name sortKey="Duparc, S" uniqKey="Duparc S">S. Duparc</name></author><author><name sortKey="Moehrle, J" uniqKey="Moehrle J">J. Moehrle</name></author><author><name sortKey="Wells, T N C" uniqKey="Wells T">T. N. C. Wells</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ginsburg, H" uniqKey="Ginsburg H">H. Ginsburg</name></author><author><name sortKey="Deharo, E" uniqKey="Deharo E">E. Deharo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guantai, E" uniqKey="Guantai E">E. Guantai</name></author><author><name sortKey="Chibale, K" uniqKey="Chibale K">K. Chibale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cruz, L R" uniqKey="Cruz L">L. R. Cruz</name></author><author><name sortKey="Spangenberg, T" uniqKey="Spangenberg T">T. Spangenberg</name></author><author><name sortKey="Lacerda, M V G" uniqKey="Lacerda M">M. V. G. Lacerda</name></author><author><name sortKey="Wells, T N C" uniqKey="Wells T">T. N. C. Wells</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Onguene, P A" uniqKey="Onguene P">P. A. Onguéné</name></author><author><name sortKey="Ntie Kang, F" uniqKey="Ntie Kang F">F. Ntie-Kang</name></author><author><name sortKey="Lifongo, L L" uniqKey="Lifongo L">L. L. Lifongo</name></author><author><name sortKey="Ndom, J C" uniqKey="Ndom J">J. C. Ndom</name></author><author><name sortKey="Sipp, W" uniqKey="Sipp W">W. Sipp</name></author><author><name sortKey="Mbaze, L M" uniqKey="Mbaze L">L. M. Mbaze</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wells, T N C" uniqKey="Wells T">T. N. C. Wells</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaur, R" uniqKey="Kaur R">R. Kaur</name></author><author><name sortKey="Arora, S" uniqKey="Arora S">S. Arora</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ayuko, T A A" uniqKey="Ayuko T">T. A. A. Ayuko</name></author><author><name sortKey="Njau, R N" uniqKey="Njau R">R. N. Njau</name></author><author><name sortKey="Cornelius, W" uniqKey="Cornelius W">W. Cornelius</name></author><author><name sortKey="Leah, N" uniqKey="Leah N">N. Leah</name></author><author><name sortKey="Ndiege, I O" uniqKey="Ndiege I">I. O. Ndiege</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bero, J" uniqKey="Bero J">J. Bero</name></author><author><name sortKey="Frederich, M" uniqKey="Frederich M">M. Frédérich</name></author><author><name sortKey="Quetin Leclercq, J" uniqKey="Quetin Leclercq J">J. Quetin-Leclercq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bhatnagar, S" uniqKey="Bhatnagar S">S. Bhatnagar</name></author><author><name sortKey="Das, P" uniqKey="Das P">P. Das</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ntie Kang, F" uniqKey="Ntie Kang F">F. Ntie-Kang</name></author><author><name sortKey="Lifongo, L L" uniqKey="Lifongo L">L. L. Lifongo</name></author><author><name sortKey="Mbaze, L M" uniqKey="Mbaze L">L. M. Mbaze</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schwikkard, S" uniqKey="Schwikkard S">S. Schwikkard</name></author><author><name sortKey="Van Heerden, F R" uniqKey="Van Heerden F">F. R. Van Heerden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, G" uniqKey="Ma G">G. Ma</name></author><author><name sortKey="Sun, Z" uniqKey="Sun Z">Z. Sun</name></author><author><name sortKey="Sun, Z" uniqKey="Sun Z">Z. Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kouam, S F" uniqKey="Kouam S">S. F. Kouam</name></author><author><name sortKey="Ngouonpe, A W" uniqKey="Ngouonpe A">A. W. Ngouonpe</name></author><author><name sortKey="Lamshoft, M" uniqKey="Lamshoft M">M. Lamshöft</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jonville, M C" uniqKey="Jonville M">M.-C. Jonville</name></author><author><name sortKey="Dive, G" uniqKey="Dive G">G. Dive</name></author><author><name sortKey="Angenot, L" uniqKey="Angenot L">L. Angenot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muganza, D M" uniqKey="Muganza D">D. M. Muganza</name></author><author><name sortKey="Fruth, B" uniqKey="Fruth B">B. Fruth</name></author><author><name sortKey="Nzunzu, J L" uniqKey="Nzunzu J">J. L. Nzunzu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dua, V K" uniqKey="Dua V">V. K. Dua</name></author><author><name sortKey="Verma, G" uniqKey="Verma G">G. Verma</name></author><author><name sortKey="Singh, B" uniqKey="Singh B">B. Singh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheenpracha, S" uniqKey="Cheenpracha S">S. Cheenpracha</name></author><author><name sortKey="Boapun, P" uniqKey="Boapun P">P. Boapun</name></author><author><name sortKey="Limtharakul Nee Ritthiwigrom, T" uniqKey="Limtharakul Nee Ritthiwigrom T">T. Limtharakul Née Ritthiwigrom</name></author><author><name sortKey="Laphookhieo, S" uniqKey="Laphookhieo S">S. Laphookhieo</name></author><author><name sortKey="Pyne, S G" uniqKey="Pyne S">S. G. Pyne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pan, L" uniqKey="Pan L">L. Pan</name></author><author><name sortKey="Mu Oz Acu A, U" uniqKey="Mu Oz Acu A U">U. Muñoz Acuña</name></author><author><name sortKey="Chai, H" uniqKey="Chai H">H. Chai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheenpracha, S" uniqKey="Cheenpracha S">S. Cheenpracha</name></author><author><name sortKey="Ritthiwigrom, T" uniqKey="Ritthiwigrom T">T. Ritthiwigrom</name></author><author><name sortKey="Laphookhieo, S" uniqKey="Laphookhieo S">S. Laphookhieo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dos Santos Torres, Z" uniqKey="Dos Santos Torres Z">Z. dos Santos Torres</name></author><author><name sortKey="Silveira, E" uniqKey="Silveira E">E. Silveira</name></author><author><name sortKey="Rocha E Silva, L" uniqKey="Rocha E Silva L">L. Rocha e Silva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tchinda, A T" uniqKey="Tchinda A">A. T. Tchinda</name></author><author><name sortKey="Jansen, O" uniqKey="Jansen O">O. Jansen</name></author><author><name sortKey="Nyemb, J N" uniqKey="Nyemb J">J.-N. Nyemb</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amelia, P" uniqKey="Amelia P">P. Amelia</name></author><author><name sortKey="Nugroho, A E" uniqKey="Nugroho A">A. E. Nugroho</name></author><author><name sortKey="Hirasawa, Y" uniqKey="Hirasawa Y">Y. Hirasawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kubo, M" uniqKey="Kubo M">M. Kubo</name></author><author><name sortKey="Yatsuzuka, W" uniqKey="Yatsuzuka W">W. Yatsuzuka</name></author><author><name sortKey="Matsushima, S" uniqKey="Matsushima S">S. Matsushima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fadaeinasab, M" uniqKey="Fadaeinasab M">M. Fadaeinasab</name></author><author><name sortKey="Taha, H" uniqKey="Taha H">H. Taha</name></author><author><name sortKey="Fauzi, P N" uniqKey="Fauzi P">P. N. Fauzi</name></author><author><name sortKey="Ali, H M" uniqKey="Ali H">H. M. Ali</name></author><author><name sortKey="Widyawaruyanti, A" uniqKey="Widyawaruyanti A">A. Widyawaruyanti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nasrullah, A" uniqKey="Nasrullah A">A. Nasrullah</name></author><author><name sortKey="Zahari, A" uniqKey="Zahari A">A. Zahari</name></author><author><name sortKey="Mohamad, J" uniqKey="Mohamad J">J. Mohamad</name></author><author><name sortKey="Awang, K" uniqKey="Awang K">K. Awang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malebo, H M" uniqKey="Malebo H">H. M. Malebo</name></author><author><name sortKey="Wenzler, T" uniqKey="Wenzler T">T. Wenzler</name></author><author><name sortKey="Cal, M" uniqKey="Cal M">M. Cal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goodman, C D" uniqKey="Goodman C">C. D. Goodman</name></author><author><name sortKey="Austarheim, I" uniqKey="Austarheim I">I. Austarheim</name></author><author><name sortKey="Mollard, V" uniqKey="Mollard V">V. Mollard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Omole, R A" uniqKey="Omole R">R. A. Omole</name></author><author><name sortKey="Gathirwa, J" uniqKey="Gathirwa J">J. Gathirwa</name></author><author><name sortKey="Akala, H" uniqKey="Akala H">H. Akala</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zahari, A" uniqKey="Zahari A">A. Zahari</name></author><author><name sortKey="Ablat, A" uniqKey="Ablat A">A. Ablat</name></author><author><name sortKey="Sivasothy, Y" uniqKey="Sivasothy Y">Y. Sivasothy</name></author><author><name sortKey="Mohamad, J" uniqKey="Mohamad J">J. Mohamad</name></author><author><name sortKey="Choudhary, M I" uniqKey="Choudhary M">M. I. Choudhary</name></author><author><name sortKey="Awang, K" uniqKey="Awang K">K. Awang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, J" uniqKey="Li J">J. Li</name></author><author><name sortKey="Seupel, R" uniqKey="Seupel R">R. Seupel</name></author><author><name sortKey="Feineis, D" uniqKey="Feineis D">D. Feineis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bringmann, G" uniqKey="Bringmann G">G. Bringmann</name></author><author><name sortKey="Lombe, B K" uniqKey="Lombe B">B. K. Lombe</name></author><author><name sortKey="Steinert, C" uniqKey="Steinert C">C. Steinert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bringmann, G" uniqKey="Bringmann G">G. Bringmann</name></author><author><name sortKey="Zhang, G" uniqKey="Zhang G">G. Zhang</name></author><author><name sortKey="Buttner, T" uniqKey="Buttner T">T. Büttner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baghdikian, B" uniqKey="Baghdikian B">B. Baghdikian</name></author><author><name sortKey="Mahiou Leddet, V" uniqKey="Mahiou Leddet V">V. Mahiou-Leddet</name></author><author><name sortKey="Bory, S" uniqKey="Bory S">S. Bory</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jaidee, A" uniqKey="Jaidee A">A. Jaidee</name></author><author><name sortKey="Promchai, T" uniqKey="Promchai T">T. Promchai</name></author><author><name sortKey="Trisuwan, K" uniqKey="Trisuwan K">K. Trisuwan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zahari, A" uniqKey="Zahari A">A. Zahari</name></author><author><name sortKey="Cheah, F" uniqKey="Cheah F">F. Cheah</name></author><author><name sortKey="Mohamad, J" uniqKey="Mohamad J">J. Mohamad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gontijo, D C" uniqKey="Gontijo D">D. C. Gontijo</name></author><author><name sortKey="Brandao, G C" uniqKey="Brandao G">G. C. Brandão</name></author><author><name sortKey="Nascimento, M F A D" uniqKey="Nascimento M">M. F. A. D. Nascimento</name></author><author><name sortKey="Oliveira, A B D" uniqKey="Oliveira A">A. B. D. Oliveira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Omar, H" uniqKey="Omar H">H. Omar</name></author><author><name sortKey="Fadaeinasa, M" uniqKey="Fadaeinasa M">M. Fadaeinasa</name></author><author><name sortKey="Taha, H" uniqKey="Taha H">H. Taha</name></author><author><name sortKey="Widyawaruyanti, A" uniqKey="Widyawaruyanti A">A. Widyawaruyanti</name></author><author><name sortKey="Nafiah, M A" uniqKey="Nafiah M">M. A. Nafiah</name></author><author><name sortKey="Rachmatiah, T" uniqKey="Rachmatiah T">T. Rachmatiah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wangchuk, P" uniqKey="Wangchuk P">P. Wangchuk</name></author><author><name sortKey="Keller, P A" uniqKey="Keller P">P. A. Keller</name></author><author><name sortKey="Pyne, S G" uniqKey="Pyne S">S. G. Pyne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lang, L" uniqKey="Lang L">L. Lang</name></author><author><name sortKey="Hu, Q" uniqKey="Hu Q">Q. Hu</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Promchai, T" uniqKey="Promchai T">T. Promchai</name></author><author><name sortKey="Jaidee, A" uniqKey="Jaidee A">A. Jaidee</name></author><author><name sortKey="Cheenpracha, S" uniqKey="Cheenpracha S">S. Cheenpracha</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Le, P M" uniqKey="Le P">P. M. Le</name></author><author><name sortKey="Srivastava, V" uniqKey="Srivastava V">V. Srivastava</name></author><author><name sortKey="Nguyen, T T" uniqKey="Nguyen T">T. T. Nguyen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hao, B" uniqKey="Hao B">B. Hao</name></author><author><name sortKey="Shen, S F" uniqKey="Shen S">S.-F. Shen</name></author><author><name sortKey="Zhao, Q J" uniqKey="Zhao Q">Q.-J. Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Presley, C C" uniqKey="Presley C">C. C. Presley</name></author><author><name sortKey="Krai, P" uniqKey="Krai P">P. Krai</name></author><author><name sortKey="Dalal, S" uniqKey="Dalal S">S. Dalal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cho, N" uniqKey="Cho N">N. Cho</name></author><author><name sortKey="Du, Y" uniqKey="Du Y">Y. Du</name></author><author><name sortKey="Valenciano, A L" uniqKey="Valenciano A">A. L. Valenciano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gonring Salarini, K L" uniqKey="Gonring Salarini K">K. L. Gonring-Salarini</name></author><author><name sortKey="Conti, R" uniqKey="Conti R">R. Conti</name></author><author><name sortKey="De Andrade, J P" uniqKey="De Andrade J">J. P. de Andrade</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tuenter, E" uniqKey="Tuenter E">E. Tuenter</name></author><author><name sortKey="Segers, K" uniqKey="Segers K">K. Segers</name></author><author><name sortKey="Kang, K B" uniqKey="Kang K">K. B. Kang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tuenter, E" uniqKey="Tuenter E">E. Tuenter</name></author><author><name sortKey="Exarchou, V" uniqKey="Exarchou V">V. Exarchou</name></author><author><name sortKey="Balde, A" uniqKey="Balde A">A. Baldé</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tuenter, E" uniqKey="Tuenter E">E. Tuenter</name></author><author><name sortKey="Ahmad, R" uniqKey="Ahmad R">R. Ahmad</name></author><author><name sortKey="Foubert, K" uniqKey="Foubert K">K. Foubert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, R" uniqKey="Kumar R">R. Kumar</name></author><author><name sortKey="Duffy, S" uniqKey="Duffy S">S. Duffy</name></author><author><name sortKey="Avery, V M" uniqKey="Avery V">V. M. Avery</name></author><author><name sortKey="Carroll, A R" uniqKey="Carroll A">A. R. Carroll</name></author><author><name sortKey="Davis, R A" uniqKey="Davis R">R. A. Davis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rasamison, V E" uniqKey="Rasamison V">V. E. Rasamison</name></author><author><name sortKey="Brodie, P J" uniqKey="Brodie P">P. J. Brodie</name></author><author><name sortKey="Merino, E F" uniqKey="Merino E">E. F. Merino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Levrier, C" uniqKey="Levrier C">C. Levrier</name></author><author><name sortKey="Balastrier, M" uniqKey="Balastrier M">M. Balastrier</name></author><author><name sortKey="Beattie, K D" uniqKey="Beattie K">K. D. Beattie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, C" uniqKey="Wang C">C. Wang</name></author><author><name sortKey="Wan, J" uniqKey="Wan J">J. Wan</name></author><author><name sortKey="Mei, Z" uniqKey="Mei Z">Z. Mei</name></author><author><name sortKey="Xang, X" uniqKey="Xang X">X. Xang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Teng, W C" uniqKey="Teng W">W.-C. Teng</name></author><author><name sortKey="Chan, W" uniqKey="Chan W">W. Chan</name></author><author><name sortKey="Suwanarusk, R" uniqKey="Suwanarusk R">R. Suwanarusk</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Evid Based Complement Alternat Med</journal-id><journal-id journal-id-type="iso-abbrev">Evid Based Complement Alternat Med</journal-id><journal-id journal-id-type="publisher-id">ECAM</journal-id><journal-title-group><journal-title>Evidence-based Complementary and Alternative Medicine : eCAM</journal-title></journal-title-group><issn pub-type="ppub">1741-427X</issn><issn pub-type="epub">1741-4288</issn><publisher><publisher-name>Hindawi</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32104196</article-id><article-id pub-id-type="pmc">7037883</article-id><article-id pub-id-type="doi">10.1155/2020/8749083</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title>Alkaloids from Plants with Antimalarial Activity: A Review of Recent Studies</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0001-8505-1795</contrib-id><name><surname>Uzor</surname><given-names>Philip F.</given-names></name><email>philip.uzor@unn.edu.ng</email><xref ref-type="aff" rid="I1"></xref></contrib></contrib-group><aff id="I1">Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, 410001 Nsukka, Enugu State, Nigeria</aff><author-notes><fn fn-type="other"><p>Academic Editor: Ghee T. Tan</p></fn></author-notes><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>12</day><month>2</month><year>2020</year></pub-date><pub-date pub-type="pmc-release"><day>12</day><month>2</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>2020</volume><elocation-id>8749083</elocation-id><history><date date-type="received"><day>9</day><month>3</month><year>2019</year></date><date date-type="rev-recd"><day>4</day><month>1</month><year>2020</year></date><date date-type="accepted"><day>21</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>Copyright © 2020 Philip F. Uzor.</copyright-statement><copyright-year>2020</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Malaria is one of the major health problems in developing countries. The disease kills a large number of people every year and also affects financial status of many countries. Resistance of the plasmodium parasite, the causative agent, to the existing drugs, including chloroquine, mefloquine, and artemisinin based combination therapy (ACT), is a serious global issue in malaria treatment and control. This warrants an urgent quest for novel compounds, particularly from natural sources such as medicinal plants. Alkaloids have over the years been recognized as important phytoconstituents with interesting biological properties. In fact, the first successful antimalarial drug was quinine, an alkaloid, which was extracted from Cinchona tree. In the present review work, the alkaloids isolated and reported recently (2013 till 2019) to possess antimalarial activity are presented. Several classes of alkaloids, including terpenoidal, indole, bisindole, quinolone, and isoquinoline alkaloids, were identified with a promising antimalarial activity. It is hoped that the reports of the review work will spur further research into the structural modification and/or development of the interesting compounds as novel antimalarial drugs.</p></abstract></article-meta></front><body><sec id="sec1"><title>1. Introduction</title><p>Malaria is an extremely dangerous parasitic disease with ravaging effects in several parts of the world. The World Health Organization (WHO) estimate shows that approximately 3.3 billion people are living at risk places of malaria. Nearly 80% of cases and 90% of deaths are reported from sub-Saharan Africa and children under the age of 5 years and pregnant women are severely affected [<xref rid="B1" ref-type="bibr">1</xref>, <xref rid="B2" ref-type="bibr">2</xref>]. In 2016, it was estimated that there were 216 million cases of malaria globally and 445,000 deaths due to malaria [<xref rid="B3" ref-type="bibr">3</xref>]. Five protozoan species of the genus <italic>Plasmodium</italic> (<italic>Plasmodium falciparum</italic>, <italic>Plasmodium malariae, Plasmodium ovale</italic>, <italic>Plasmodium vivax</italic>, and <italic>P. knowlesi</italic>) are responsible for human malaria, although the majority of malarial infections are caused by <italic>P. falciparum</italic> and <italic>P. vivax.</italic> While <italic>P. vivax</italic> is less dangerous but more widespread, <italic>P. falciparum</italic> is fatal and is predominant in Africa [<xref rid="B1" ref-type="bibr">1</xref>, <xref rid="B4" ref-type="bibr">4</xref>].</p><p>Malaria has been treated with quinine, chloroquine, amodiaquine, mefloquine, and artemisinin derivatives (<xref ref-type="fig" rid="fig1">Figure 1</xref>), among other drugs. The alkaloidal drug, quinine, is the first antimalarial drug isolated from Cinchona bark. The drug is still quite useful in the treatment of multidrug-resistant malaria. Chloroquine, a 4-aminoquinoline, was developed in the 1940s as a synthetic derivative from quinine. It was effective, cheap, and less toxic and was the drug of choice for malarial treatment for decades; however, its use has been restricted in modern malaria therapy due to parasite resistance to the drug [<xref rid="B5" ref-type="bibr">5</xref>, <xref rid="B6" ref-type="bibr">6</xref>]. Mefloquine is structurally related to quinine and has been introduced to treat chloroquine-resistant malaria, though its use is limited because of resistance and neuropsychiatric side effects [<xref rid="B7" ref-type="bibr">7</xref>]. Artemisinin is a natural endoperoxide isolated from sweet warm wood plant <italic>Artemisia annua.</italic> Artemisinin and its semisynthetic analogs artemether, artether, and artesunate are potent antimalarial agents especially used in the regions where the resistance has developed to other antimalarial agents. The WHO recommends the use of artemisinin analogs in combination with other drugs (ACT) for the treatment of malaria in order to control resistance. Unfortunately, there have been reports of parasite resistance to the ACT [<xref rid="B8" ref-type="bibr">8</xref>].</p><p>Given the development of resistance of the malarial parasites against many of the current treatment regimens, there has been urgent quest to identify new antimalarial chemotherapeutic agents from natural sources, particularly medicinal plants, in order to possibly avoid problems related to drug resistance [<xref rid="B9" ref-type="bibr">9</xref>–<xref rid="B14" ref-type="bibr">14</xref>]. This is due to the widespread use of plant materials in the treatment of malaria in many traditional medical practices together with the fact that plants were the sources of the two prominent antimalarial lead compounds, quinine and artemisinin.</p><p>Several classes of phytoconstituents are responsible for the antimalarial activity of plants including alkaloids, terpenes, steroids, and flavonoids. Alkaloids are considered as an important group exhibiting diverse biological activities, particularly antimalarial activity. They constitute an important class of structurally diversified compounds that are having the nitrogen atom in the heterocyclic ring and are derived from the amino acids [<xref rid="B15" ref-type="bibr">15</xref>]. Large numbers of alkaloids have been isolated from different plant sources and reported for their potent antimalarial activity, some of which have been previously reviewed up till the year 2012 [<xref rid="B1" ref-type="bibr">1</xref>, <xref rid="B13" ref-type="bibr">13</xref>, <xref rid="B16" ref-type="bibr">16</xref>–<xref rid="B20" ref-type="bibr">20</xref>]. However, more updates on the current research on alkaloids as potential antimalarial agents are needed. In the present review work, alkaloids from medicinal plants with antimalarial property which are reported recently from 2013 to 2019 are summarized. They are discussed in subclasses of alkaloids and the chemical structures of the newly reported compounds and those with antiplasmodial activity are shown in the figures according to their subclasses.</p><sec id="sec1.1"><title>1.1. Terpenoidal and Steroidal Alkaloids</title><p>Several alkaloids having varying terpenoidal backbone, including the cassane-type diterpenes, indoloterpene, and bisindolomonoterpenic alkaloids, have been isolated recently from medicinal plants (<italic>Caesalpinia minax</italic>, <italic>Polyalthia oliveri</italic>, and <italic>Strychnos nux-vomica</italic>) and shown to possess good antiplasmodial activity (<xref ref-type="fig" rid="fig2">Figure 2</xref>).</p><p>Ma et al. [<xref rid="B21" ref-type="bibr">21</xref>] isolated two new diterpene alkaloids, caesalminines A (<bold>1</bold>) and B (<bold>2</bold>), possessing a tetracyclic cassane-type diterpenoid skeleton with <italic>γ</italic>-lactam ring from the seeds of <italic>Caesalpinia minax</italic> (Fabaceae). Compounds <bold>1</bold> and <bold>2</bold> exhibit antiplasmodial activity with IC<sub>50</sub> values of 0.42 and 0.79 <italic>μ</italic>M, respectively. Substitution of the amino hydrogen of the diterpenoid (in compound <bold>1)</bold> with the alcoholic group (C<sub>2</sub>H<sub>5</sub>OH) produced a compound (<bold>2</bold>) with slightly reduced antiplasmodial activity. In another study, three new indolosesquiterpene alkaloids, 8<italic>α</italic>-polyveolinone (<bold>3</bold>), <italic>N</italic>-acetyl-8<italic>α</italic>-polyveolinone (<bold>4</bold>), and <italic>N</italic>-acetyl-polyveoline (<bold>5</bold>), together with three known compounds, were isolated from the stem bark of <italic>Polyalthia oliveri</italic> (Annonaceae) by Kouam et al. [<xref rid="B22" ref-type="bibr">22</xref>]. Compounds <bold>4</bold> and <bold>5</bold> exhibit moderate antiplasmodial activity against <italic>P. falciparum</italic> NF54 strain with low cytotoxicity on l myoblast (L6) cell line. In a related study of another plant in the same family, three bisindolomonoterpenic alkaloids, together with the known compound, strychnochrysine (<bold>6</bold>), were isolated from the stem bark of <italic>Strychnos nux-vomica</italic> L. (Loganiaceae). These longicaudatine-type alkaloids display antiplasmodial activity against both the chloroquine-resistant and chloroquine-sensitive strains. The most interesting was compound <bold>6</bold> with an IC<sub>50</sub> value at around 10 <italic>μ</italic>M [<xref rid="B23" ref-type="bibr">23</xref>]. Muganza et al. [<xref rid="B24" ref-type="bibr">24</xref>] reported the isolation of two known indolosesquiterpene alkaloids, polyalthenol (<bold>7</bold>) and <italic>N</italic>-acetyl-polyveoline (<bold>5</bold>), from various parts of the tree <italic>Greenwayodendron suaveolens</italic> (Engl. & Diels) Verdc. (syn. <italic>Polyalthia suaveolens</italic> Engl. & Diels) (Annonaceae). The highest selectivity was observed for compound <bold>5</bold> against <italic>P. falciparum</italic> K1 (IC<sub>50</sub> 2.8 <italic>μ</italic>M, selectivity index 10.9).</p><p>Alkaloids having steroidal nucleus have also been isolated and shown to possess antimalarial activity. Dua et al. [<xref rid="B25" ref-type="bibr">25</xref>] investigated the <italic>in vitro</italic> antimalarial and cytotoxic effects of the known compound, conessine (<bold>8</bold>), which was isolated from the plant <italic>Holarrhena antidysenterica</italic>. The four-day <italic>in vivo</italic> test was also used to test for the antimalarial activity against a chloroquine-sensitive <italic>P. berghei</italic> NK65 strain in BALB/c mice. Compound (<bold>8</bold>) shows <italic>in vitro</italic> antiplasmodial activity with its IC<sub>50</sub> values of 1.9 <italic>μ</italic>g/ml and 1.3 <italic>μ</italic>g/ml in the schizont maturation and pLDH assays, respectively, and cytotoxicity IC<sub>50</sub> of 14 <italic>μ</italic>g/ml. The compound also significantly reduces parasitaemia (88.95% parasite inhibition) in <italic>P. berghei</italic>-infected mice. In addition, the phytochemical investigation of an alkaloidal extract of the related plant <italic>Holarrhena pubescens</italic> roots led to the isolation of a new pregnene-type alkaloid, mokluangin D (<bold>9</bold>), together with nine known steroidal alkaloids. Two of the known compounds, irehline (<bold>10</bold>) and mokluangin A (<bold>11</bold>), show most potent antimalarial activity against <italic>P. falciparum</italic> K1 strain (a multidrug-resistant strain) with IC<sub>50</sub> values of 1.2 and 2.0 <italic>μ</italic>M, respectively, and weak cytotoxic activity (27.7 and 30.6 <italic>μ</italic>M, respectively) against the NCI-H187 cell line. Five other compounds show moderate activity. Compound <bold>9</bold> was not tested. A study of the structure activity relationships in these compounds (illustrated with compound <bold>11</bold>) indicates that the C-3 amino group, the nature of the E ring, and the carbonyl group at C-18 are important for the activity against the <italic>P. falciparum</italic> K1 strain [<xref rid="B26" ref-type="bibr">26</xref>]. Furthermore, Pan et al. [<xref rid="B27" ref-type="bibr">27</xref>] reported the isolation of a known buxus alkaloid, <italic>N</italic>-3-benzoyldihydrocyclomicrophylline F (<bold>12</bold>), together with other compounds from <italic>Buxus cochinchinensis</italic> Pierre ex Gagnep. (Buxaceae). The buxus alkaloid (<bold>12)</bold> was found to show significant <italic>in vitro</italic> antimalarial activity against the drug-resistant Dd2 strain of <italic>P. falciparum</italic> with IC<sub>50</sub> value of 2.07 <italic>μ</italic>M (cytotoxicity against HT-29 human carcinoma is 1.9 <italic>μ</italic>M and against NF-KB is >20).</p></sec><sec id="sec1.2"><title>1.2. Indole Alkaloids</title><p>A number of indole alkaloids (<xref ref-type="fig" rid="fig3">Figure 3</xref>) have been isolated recently and shown to possess potent antiplasmodial activity.</p><p>Chemical investigation of <italic>Alstonia macrophylla</italic> bark led to the isolation of two new nitrogenous derivatives, alstoniaphyllines A (<bold>13</bold>) and B (<bold>14</bold>), a new indole alkaloid, alstoniaphylline C (<bold>15</bold>), and eight known alkaloids including alstonisine (<bold>16</bold>). Compound <bold>16</bold> exhibits antiplasmodial activity against <italic>P. falciparum</italic>, with an IC<sub>50</sub> value of 7.6 <italic>μ</italic>M [<xref rid="B28" ref-type="bibr">28</xref>]. Another new indole alkaloid, 12-hydroxy-<italic>N</italic>-acetyl-21(<italic>N</italic>)-dehydroplumeran-18-oic acid (<bold>17</bold>), and 11 known indole alkaloids including 20-epi-dasycarpidone (<bold>18</bold>) were isolated from <italic>Aspidosperma ulei</italic> Markgr. (Apocynaceae). Only compound <bold>18</bold> is active against multidrug-resistant K1 strain of <italic>P. falciparum</italic> with IC<sub>50</sub> value of 16.7 <italic>μ</italic>M. None of these compounds exhibited toxicity to fibroblasts (IC<sub>50</sub> > 50 <italic>μ</italic>g/mL) [<xref rid="B29" ref-type="bibr">29</xref>]. Also, Tchinda et al. [<xref rid="B30" ref-type="bibr">30</xref>] reported the isolation of a new bisindole alkaloid, strychnobaillonine (<bold>19</bold>), with original C-17-N-1′ and C-23-C-17′ junctions, in addition to three other known compounds from the roots of <italic>Strychnos icaja</italic>. Compound <bold>19</bold> shows potent activity against the chloroquine-sensitive 3D7 strain of <italic>P. falciparum</italic> with an IC<sub>50</sub> value of 1.1 <italic>μ</italic>M. More recently, two new sarpagine-type indole alkaloids together with five known alkaloids, including 16-demethoxycarbonylvoacamine (<bold>20</bold>), were isolated from the bark of <italic>Tabernaemontana macrocarpa</italic> Jack. Compound <bold>20</bold> shows antiplasmodial activity against <italic>P. falciparum</italic> 3D7 and cytotoxic activity against human cell line, HepG2 cells [<xref rid="B31" ref-type="bibr">31</xref>].</p></sec><sec id="sec1.3"><title>1.3. Phenanthroindolizine Alkaloids</title><p>The structures of some phenanthroindolizine alkaloids with promising antiplasmodial activity are shown in <xref ref-type="fig" rid="fig3">Figure 3</xref>. Kubo et al. [<xref rid="B32" ref-type="bibr">32</xref>] isolated a new seco-phenanthroindolizine alkaloid, 4a,b-<italic>seco</italic>-dehydroantofine (<bold>21</bold>), and three known phenanthroindolizine alkaloids, dehydrotylophorine (<bold>22</bold>), dehydroantofine (<bold>23</bold>), and tylophoridicine D (<bold>24</bold>), from the twigs of <italic>Ficus septica.</italic> While compound <bold>21</bold> exhibits a moderate antimalarial activity against the 3D7 strain of <italic>P. falciparum</italic> with IC<sub>50</sub> value 4.0 <italic>μ</italic>M, the known alkaloids (<bold>22</bold>–<bold>24</bold>) display strong activity with IC<sub>50</sub> values of 0.42, 0.028, and 0.058 <italic>μ</italic>M, respectively. The cytotoxicities of the compounds (<bold>21</bold>–<bold>24)</bold> against mouse fibroblast cells L929 are >56 (SI ≥ 14), 8.2 (SI = 19.5), >55 (SI ≥ 1964), and >56 <italic>μ</italic>M (SI ≥ 966), respectively. Compounds <bold>23</bold> and <bold>24</bold> (particularly <bold>23</bold>) exhibit the highest selectivity against the malaria parasite. From the structure activity relationship, opening of ring A (present in compound <bold>21</bold>) possibly reduces antiplasmodial activity, while the four methoxy substituents at rings D and E (present in compound <bold>23</bold>) could be essential for activity.</p></sec><sec id="sec1.4"><title>1.4. Isoquinoline, Benzylisoquinoline, and Hasubanane Alkaloids</title><p>Isoquinoline and related alkaloids with antiplasmodial activity have also been isolated. The structures of some of them are shown in <xref ref-type="fig" rid="fig4">Figure 4</xref>.</p><p>Fadaeinasab et al. [<xref rid="B33" ref-type="bibr">33</xref>] isolated seven isoquinoline alkaloids from the bark of <italic>Actinodaphne macrophylla</italic>. They display <italic>in vitro</italic> antiplasmodial activity against <italic>P. falciparum</italic> 3D7 with IC<sub>50</sub> values ranging from 0.05 to 3.11 <italic>μ</italic>M for cycleanine (<bold>25)</bold>, 10-demethylxylopinine (<bold>26</bold>), reticuline (<bold>27</bold>), laurotetanine (<bold>28</bold>), bicuculine (<bold>29</bold>), <italic>α</italic>-hydrastine (<bold>30</bold>), and anolobine (<bold>31</bold>), respectively. Compound <bold>26</bold> was found to be the most active. Possibly, the fusion of the two isoquinoline rings (in compound <bold>26</bold>) enhances antiplasmodial activity. In another study, Nasrullah et al. [<xref rid="B34" ref-type="bibr">34</xref>] isolated four known alkaloids: (+)-<italic>N</italic>-methylisococlaurine (<bold>32</bold>), atherosperminine (<bold>33</bold>), 2-hydroxyathersperminine (<bold>34</bold>), and noratherosperminine (<bold>35</bold>) from the stem bark of <italic>Cryptocarya nigra</italic>. Compounds <bold>32</bold>, <bold>33</bold>, and <bold>34</bold> show strong antiplasmodial activity against a chloroquine-resistant strain of <italic>P. falciparum</italic> (K1 strain) with IC<sub>50</sub> values of 5.40, 5.80, and 0.75 <italic>μ</italic>M, respectively. Compound <bold>35</bold> was not tested. The <italic>N</italic>,<italic>N</italic>-dimethyl groups of the ethylamine side chain (in compounds <bold>33</bold> and <bold>34</bold>) are, perhaps, essential for antiplasmodial activity. Malebo et al. [<xref rid="B35" ref-type="bibr">35</xref>] also isolated four pure alkaloids including palmatine (<bold>36</bold>) and mixtures of alkaloids from the leaves of <italic>Annickia kummeriae</italic>. The alkaloids exhibit low cytotoxicity (IC<sub>50</sub> 30–>90 <italic>μ</italic>g/ml) and strong-to-moderate antiplasmodial activity (IC<sub>50</sub> 0.08 ± 0.001–2.4 ± 0.642 <italic>μ</italic>g/ml, SI 1.5–1154). Compound <bold>36</bold> exhibits the highest activity against <italic>P. falciparum</italic> K1 (IC<sub>50</sub> 0.080 ± 0.001 <italic>μ</italic>g/mL, selectivity index (SI) = 1154). Further, three known compounds, dihydronitidine (<bold>37</bold>), pellitorine (<bold>38</bold>), and heitziquinone (<bold>39</bold>), with antiparasitic activity were identified in <italic>Zanthoxylum heitzii</italic> (Rutaceae) bark extract. Compound <bold>37</bold> is the most active compound with an IC<sub>50</sub> value of 0.0089 <italic>μ</italic>g/ml (25 nM), though it is slower in action, while compounds <bold>38</bold> and <bold>39</bold> are less potent, with IC<sub>50</sub> values of 9.7 ± 1.6 <italic>μ</italic>M and 8.8 ± 0.5 <italic>μ</italic>M, but they are are fast-acting [<xref rid="B36" ref-type="bibr">36</xref>].</p><p>The structures of bisbenzylisoquinoline and hasubanane alkaloids with antiplasmodial activity are shown in <xref ref-type="fig" rid="fig5">Figure 5</xref>.</p><p>From the leaves of <italic>Stephania abyssinica</italic>, two bisbenzylisoquinoline alkaloids, (−)-pseudocurine (<bold>40</bold>) and (−)-pseudoisocurine (<bold>41</bold>), and one hasubanane alkaloid, (−)-10-oxoaknadinine (<bold>42</bold>), were isolated. Compound <bold>40</bold> exhibits strong antiplasmodial activity against both chloroquine-susceptible D6 and resistant W2 strains of <italic>P. falciparum</italic> (IC<sub>50</sub> 0.29 ± 0.00 and 0.31 ± 0.01 <italic>μ</italic>g/ml, respectively). Compound <bold>41</bold> shows moderate and mild activity (0.75 ± 0.11 and 1.65 ± 0.03 <italic>μ</italic>g/ml, respectively) and compound <bold>42</bold> shows mild activity against W2 (IC<sub>50</sub> = 3.45 <italic>μ</italic>g/ml) but was inactive against D6 (IC<sub>50</sub> = 10.25 <italic>μ</italic>g/ml) [<xref rid="B37" ref-type="bibr">37</xref>]. Also, six alkaloids were isolated from <italic>Alseodaphne corneri.</italic> These include (+)-laurotetanine (<bold>43</bold>) and (+)-norstephasubine (<bold>44</bold>), both of which exhibit strong antiplasmodial activity with IC<sub>50</sub> values of 0.189 and 0.116 <italic>μ</italic>M, respectively [<xref rid="B38" ref-type="bibr">38</xref>].</p></sec><sec id="sec1.5"><title>1.5. Naphthoisoquinoline Alkaloids</title><p>Naphthoisoquinoline alkaloids have also been reported recently, many of which are dimeric. Naphthoisoquinoline alkaloids are usually characterized by the C5/C8′ linkage between the naphthalene and the isoquinoline portions of these alkaloids. Dioncophyllaceous alkaloids possess naphthoisoquinoline nucleus. Dioncophylline F (<bold>45</bold>), the first 5,8′-coupled dioncophyllaceous alkaloid (i.e., lacking an oxygen function at C-6 and possessing an <italic>R</italic>-configuration at C-3), was isolated from Congolese liana <italic>Ancistrocladus ileboensis</italic> with some other alkaloids. The alkaloids show high and specific activities against <italic>P. falciparum</italic> [<xref rid="B39" ref-type="bibr">39</xref>]. In addition, dimeric naphthoisoquinoline alkaloids were reported from the Ancistrocladus species. Mbandakamines A (<bold>46</bold>) and B (<bold>47</bold>) were isolated from the leaves of a Congolese Ancistrocladus species as the first dimeric naphthylisoquinoline alkaloids with an unsymmetrically coupled central biaryl axis (<xref ref-type="fig" rid="fig6">Figure 6</xref>). Mbandakamine A (<bold>46</bold>) exhibits good antimalarial activity [<xref rid="B40" ref-type="bibr">40</xref>].</p><p>In a related study on the root bark of the same plant, Ancistrocladus species from the Democratic Republic of Congo, a new dimeric naphthylisoquinoline alkaloid, jozimine A2(<bold>48</bold>), was isolated. Compound <bold>48</bold> is one of the as yet very rare naphthylisoquinoline dimers whose central biaryl axis is rotationally hindered. Moreover, it is the first natural dimer of a dioncophyllaceae-type alkaloid that is lacking oxygen functions at C6 and bearing <italic>R</italic> configurations at C3 in its two isoquinoline portions. The new dimer (<bold>48</bold>) exhibits excellent, and specific, antiplasmodial activity [<xref rid="B41" ref-type="bibr">41</xref>].</p></sec><sec id="sec1.6"><title>1.6. Aporphine and Morphinandienone Alkaloids</title><p>Chemically, aporphine alkaloids possess a tetracyclic framework. They incorporate a tetrahydroisoquinoline substructure and belong to the isoquinoline class of alkaloids. Several aporphine alkaloids possessing antimalarial activity have been isolated recently (<xref ref-type="fig" rid="fig7">Figure 7</xref>).</p><p>A new aporphine alkaloid named vireakine (<bold>49</bold>) along with two known alkaloids, stephanine (<bold>50</bold>) and pseudopalmatine (<bold>51</bold>), described for the first time in <italic>Stephania rotunda</italic>, together with five known alkaloids, was isolated and identified. The compounds were evaluated for their <italic>in vitro</italic> antiplasmodial and cytotoxic activities. All tested compounds show significant antiplasmodial activity with IC<sub>50</sub> values ranging from 1.2 to 52.3 <italic>μ</italic>M with a good selectivity index for compound <bold>51</bold> with IC<sub>50</sub> value of 2.8 <italic>μ</italic>M against W2 strain of <italic>P. falciparum</italic> and with IC<sub>50</sub> > 25 <italic>μ</italic>M on K562S cells [<xref rid="B42" ref-type="bibr">42</xref>]. Further, from the twigs of <italic>Dasymaschalon obtusipetalum</italic>, one new p-quinonoid aporphine alkaloid, obtusipetadione (<bold>52</bold>), and eleven known compounds were isolated. Compound <bold>52</bold> shows significant <italic>in vitro</italic> antiplasmodial activity against the <italic>P. falciparum</italic> strains TM4 and K1 (multidrug-resistant strain) with IC<sub>50</sub> values of 2.46 ± 0.12 and 1.38 ± 0.99 <italic>μ</italic>g/mL, respectively, with no cytotoxicity [<xref rid="B43" ref-type="bibr">43</xref>]. In another report, six alkaloids were isolated from the bark of <italic>Dehaasia longipedicellata</italic>. All the compounds display potent-to-moderate activity against the growth of <italic>P. falciparum</italic> K1 isolate (resistant strain) with IC<sub>50</sub> values ranging from 0.031 to 30.40 <italic>μ</italic>M. Two of the compounds, a bisbenzylisoquinoline, (-)-<italic>O</italic>, <italic>O′</italic>-dimethylgrisabine (<bold>53</bold>), and a morphinadienone, (-)-milonine (<bold>54</bold>), were the most potent compounds, with IC<sub>50</sub> values of 0.031 and 0.097 <italic>μ</italic>M, respectively, which are comparable to the standard, chloroquine (0.090 <italic>μ</italic>M). All of the compounds showed no potency against lung (A549) cancer cells and weak cytotoxicity against skin (A375) cancer cells [<xref rid="B44" ref-type="bibr">44</xref>]. Further, two aporphine alkaloids and other compounds were isolated from <italic>Xylopia sericea</italic> leaves. One of the aporphine alkaloids, anonaine (<bold>55</bold>), shows significant antiplasmodial effect against chloroquine-resistant W2 strain <italic>P. falciparum</italic> and moderate cytotoxicity against HepG2 cells (IC<sub>50</sub> 23.2 ± 2.7 <italic>μ</italic>g/ml, CC<sub>50</sub> 38.3 ± 2.3 <italic>μ</italic>g/ml, SI 1.6) [<xref rid="B45" ref-type="bibr">45</xref>]. Also, one new aporphine named tavoyanine A (<bold>56</bold>), along with four known aporphines, three of which are roemerine (<bold>57</bold>), laurolitsine (<bold>58</bold>), and boldine (<bold>59</bold>), and one morphinandienone type, sebiferine (<bold>60</bold>), were isolated from the leaves of <italic>Phoebe tavoyana</italic> (Meissn.) Hook f. (Lauraceae). Compounds <bold>56</bold>–<bold>60</bold> were found to exhibit potent inhibitory activity against the growth of <italic>P. falciparum</italic> 3D7 clone, with IC<sub>50</sub> values of 0.89, 1.49, 1.65, and 2.76 <italic>μ</italic>g/ml, respectively [<xref rid="B46" ref-type="bibr">46</xref>]. Compound <bold>60</bold> was previously isolated from <italic>Dehaasia longipedicellata</italic> but was found to have moderate activity against <italic>P. falciparum</italic> KI isolate (resistant strain) with IC<sub>50</sub> value of 22.46 <italic>μ</italic>M [<xref rid="B44" ref-type="bibr">44</xref>].</p></sec><sec id="sec1.7"><title>1.7. Protoberberine Alkaloids</title><p>This class of compounds is mainly found in the plants of the Papaveraceae family. The alkaloids are characterized by a tetracyclic ring system that “hides” a substituted phenethylamine or vanillylamine, depending on the viewing “angle” (<xref ref-type="fig" rid="fig8">Figure 8</xref>).</p><p>Wangchuk et al. [<xref rid="B47" ref-type="bibr">47</xref>] carried out phytochemical studies of the aerial parts of <italic>Meconopsis simplicifolia</italic> (D. Don) Walpers (Papaveraceae), resulting in the isolation of one new protoberberine-type alkaloid, simplicifolianine (<bold>61</bold>), and five known alkaloids. Compound <bold>61</bold> displays the most potent antiplasmodial activity against the <italic>P. falciparum</italic> strains, TM4/8.2 (chloroquine-antifolate-sensitive strain) and K1CB1 (multidrug-resistant strain) with IC<sub>50</sub> values of 0.78 <italic>μ</italic>g/mL and 1.29 <italic>μ</italic>g/mL, respectively. The compounds did not show any significant cytotoxic activity against carcinoma KB cells and normal Vero cells. In another study, coptisine (<bold>62</bold>), an alkaloid from <italic>Coptidis rhizoma</italic> (Ranunculaceae), was found to be a novel and potent inhibitor of <italic>Plasmodium falciparum</italic> dihydroorotate dehydrogenase (PfDHODH) with an IC<sub>50</sub> value of 1.83 ± 0.08 <italic>μ</italic>M [<xref rid="B48" ref-type="bibr">48</xref>]. Besides, Promchai et al. [<xref rid="B49" ref-type="bibr">49</xref>] isolated five new oxoprotoberberine alkaloids, miliusacunines A–E (<bold>63–67</bold>), along with nine known compounds from the leaves and twigs of <italic>Miliusa cuneata</italic> (Annonaceae). All isolated compounds were evaluated for their cytotoxicity against the KB and Vero cell lines and for antimalarial activities against the <italic>P. falciparum</italic> strains TM4 and K1 (sensitive and multidrug-resistant strains, respectively). Compound <bold>63</bold> exhibits <italic>in vitro</italic> antimalarial activity against the TM4 strain, with an IC<sub>50</sub> value of 19.3 ± 3.4 <italic>μ</italic>M, while compound <bold>64</bold> demonstrates significant activity against the K1 strain, with an IC<sub>50</sub> value of 10.8 ± 4.1 <italic>μ</italic>M. Both compounds show no discernible cytotoxicity to the Vero cell line at the concentration levels evaluated. In another study, a bioassay-guided fractionation of the tubers of <italic>Stephania venosa</italic> (Blum) Spreng (Menispermaceae) led to the isolation of four aporphine and one tetrahydroprotoberberine alkaloids including stephanine (<bold>50</bold>), which was observed to be the most active antiplasmodial compound but is also the most cytotoxic with the lowest selectivity index [<xref rid="B50" ref-type="bibr">50</xref>]. Compound <bold>50</bold> was previously reported in <italic>Stephania rotunda</italic> with significant antiplasmodial activity [<xref rid="B42" ref-type="bibr">42</xref>].</p></sec><sec id="sec1.8"><title>1.8. Amaryllidaceae Alkaloids</title><p>A particular characteristic of the family of Amaryllidaceae is a consistent presence of an exclusive group of alkaloids, which have been isolated from the plants of all the genera of this family. The Amaryllidaceae alkaloids represent a large and still expanding group of isoquinoline alkaloids, the majority of which are not known to occur in any other family of plants; these alkaloids are considered to be biogenetically related (<xref ref-type="fig" rid="fig9">Figure 9</xref>).</p><p>Phytochemical investigation of the bulbs of <italic>Lycoris radiata</italic> (Fam: Amaryllidaceae) resulted in the isolation of five new Amaryllidaceae alkaloids: (+)-5,6-dehydrolycorine (<bold>68</bold>), (+)-3<italic>α</italic>,6<italic>β</italic>-diacetyl-bulbispermine (<bold>69</bold>), (+)-3<italic>α</italic>-hydroxy-6<italic>β</italic>-acetyl-bulbispermine (<bold>70</bold>), (+)-8,9-methylenedioxylhomolycorine-N-oxide (<bold>71</bold>), and 5,6-dihydro-5-methyl-2-hydroxyphenanthridine (<bold>72</bold>), together with two known compounds. Compound <bold>68</bold> exhibits antimalarial activity with IC<sub>50</sub> values of 2.3 <italic>μ</italic>M for D6 strain and 1.9 <italic>μ</italic>M for W2 strain of <italic>P. falciparum.</italic> Compound <bold>68</bold> also shows potent cytotoxicity against astrocytoma and glioma cell lines (CCF-STTG1, CHG-5, SHG-44, and U251), as well as HL-60, SMMC-7721, and W480 cell lines with IC<sub>50</sub> values of 9.4–11.6 <italic>μ</italic>M [<xref rid="B51" ref-type="bibr">51</xref>]. Also, antimalarial bioassay-guided fractionation of the swamp lily <italic>Crinum erubescens</italic> (Amaryllidaceae) led to the isolation of four compounds with potent antiplasmodial activity. They include three known compounds, cripowellin A (<bold>73</bold>), cripowellin B (<bold>74</bold>), and hippadine (<bold>75</bold>), as well as the new compounds cripowellin C (<bold>76</bold>) and D (<bold>77</bold>). The antiplasmodial activities (IC<sub>50</sub> values) of compounds <bold>73</bold>, <bold>74, 76</bold>, and <bold>77</bold> were determined to be 30 ± 2, 180 ± 20, 26 ± 2, and 260 ± 20 nM, respectively, while compound <bold>75</bold> is inactive. Their antiproliferative IC<sub>50</sub> values against the A2780 human ovarian cancer cell line were 11.1 ± 0.4, 16.4 ± 0.1, 25 ± 2, and 28 ± 1 nM, respectively. Presence of OH group in the cripowellin backbone (indicated by R in the structures of <bold>73</bold> and <bold>74</bold> or <bold>76</bold> and <bold>77</bold>) seems to enhance antiplasmodial activity [<xref rid="B52" ref-type="bibr">52</xref>].</p><p>Crinane alkaloids were also isolated from the Amaryllidaceae family. A chemical investigation of <italic>Amaryllis belladonna</italic> Steud. (Amaryllidaceae) bulbs resulted in the isolation of the new crinane alkaloid 1,4-dihydroxy-3-methoxy powellan (<bold>78</bold>), along with the three known crinane alkaloids, distichamine (<bold>79)</bold>, 11-O-acetylambelline (<bold>80</bold>), and ambelline (<bold>81</bold>), as well as the two lycorane alkaloids, acetylcaranine (<bold>82</bold>) and hippadine (<bold>75</bold>). Compund <bold>82</bold> shows the most potent inhibitory activity, with an IC<sub>50</sub> value of 3.3 ± 0.3 <italic>μ</italic>M, but compound <bold>75</bold> is inactive despite its structural similarity. Slight structural differences of conjugation and substituents in the tetrahydrophenanthridine moiety seem to greatly affect the inhibitory activity. The crinane-type alkaloid (<bold>80)</bold> exhibits weak inhibitory activity (IC<sub>50</sub>, 35 ± 1 <italic>μ</italic>M), whereas <bold>81</bold> shows stronger activity with an IC<sub>50</sub> value of 7.3 ± 0.3 <italic>μ</italic>M. The difference in the antiplasmodial activity of these two compounds could be explained by the placement of oxy-substitution at C-11, since acetylation of the oxygenated C-11 of the ethanol bridge slightly decreased the inhibitory activity. The new crinane-type alkaloid <bold>78</bold> showed weak inhibitory activity (IC<sub>50</sub>, 37 ± 3 <italic>μ</italic>M). Compound <bold>79</bold> has little inhibitory activity, despite its similarity to <bold>80</bold> and <bold>81</bold>. Only compound <bold>82</bold> shows inhibitory, though very weak, effect against A2780 ovarian cells with an IC<sub>50</sub> value of 56 ± 1 <italic>μ</italic>M [<xref rid="B53" ref-type="bibr">53</xref>]. In a recent study, lycorine (<bold>83</bold>), along with 14 other alkaloids, was isolated from <italic>Worsleya procera</italic> roots. The compound (<bold>83)</bold> exhibits antiplasmodial activity against both sensitive (3D7) and resistant (K1) <italic>P. falciparum</italic> parasite strains with IC<sub>50</sub> values of 2.5 and 3.1 <italic>μ</italic>M, respectively, and a low cytotoxic profile against human hepatocarcinoma cells (HepG2), with a selectivity index greater than 100 [<xref rid="B54" ref-type="bibr">54</xref>].</p></sec><sec id="sec1.9"><title>1.9. Cyclopeptide Alkaloids</title><p>Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a <italic>β</italic>-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more amino acid moieties [<xref rid="B55" ref-type="bibr">55</xref>]. The structures of the cyclopeptide alkaloids from plants that possess antimalarial activity are shown in <xref ref-type="fig" rid="fig10">Figure 10</xref>.</p><p>Four cyclopeptide alkaloids were isolated from the root bark of <italic>Hymenocardia acida</italic>. These include hymenocardinol (<bold>84</bold>) as well as hymenocardine <italic>N</italic>-oxide (<bold>85</bold>) and a new cyclopeptide alkaloid containing an unusual histidine moiety named hymenocardine-H (<bold>86</bold>). All the compounds show moderate antiplasmodial activity, with IC<sub>50</sub> values ranging from 12.2 to 27.9 <italic>μ</italic>M, the most active one being compound <bold>85</bold>, with an IC<sub>50</sub> value of 12.2 ± 6.6 <italic>μ</italic>M. Compounds <bold>84</bold>–<bold>86</bold> were found not to be cytotoxic against MRC-5 cells (IC<sub>50</sub> > 64.0 <italic>μ</italic>M) [<xref rid="B56" ref-type="bibr">56</xref>]. In addition, nine cyclopeptide alkaloids were isolated from the roots of <italic>Ziziphus oxyphylla</italic>. The most potent compound, <italic>O</italic>-desmethylnummularine-R (<bold>87</bold>), exhibits antiplasmodial activity with an IC<sub>50</sub> value of 3.2 ± 2.6 <italic>μ</italic>M against <italic>P. falciparum</italic> K1 and cytotoxic activity (IC<sub>50</sub> value of >64.0 <italic>μ</italic>M) against MRC-5 cells [<xref rid="B57" ref-type="bibr">57</xref>].</p></sec><sec id="sec1.10"><title>1.10. Quinoline Alkaloids</title><p>Chemical investigation of the roots of the Australian desert plant <italic>Eremophila microtheca</italic> yielded a novel quinoline-serrula alkaloid, microthecaline A (<bold>88</bold>), which displays moderate antimalarial activity against <italic>P. falciparum</italic> (3D7 strain), with an IC<sub>50</sub> value of 7.7 <italic>μ</italic>M [<xref rid="B58" ref-type="bibr">58</xref>]. In another study, seven known furoquinoline alkaloids and two known methoxyflavones were isolated from <italic>Melicope madagascariensis</italic> (Rutaceae). One of the compounds, 6-methoxy-7-hydroxydictamnine (heliparvifoline) (<bold>89</bold>), exhibits weak antimalarial activity (IC<sub>50</sub> = 35 <italic>μ</italic>M) against the chloroquine-resistant strain Dd2 of <italic>P. falciparum</italic> [<xref rid="B59" ref-type="bibr">59</xref>].</p></sec><sec id="sec1.11"><title>1.11. Pyridocoumarin Alkaloids</title><p>Chemical investigation of the aerial parts of <italic>Goniothalamus australis</italic> resulted in the isolation of two pyridocoumarin alkaloids, goniothalines A (<bold>90</bold>) and B (<bold>91</bold>), as well as eight known natural products, including sauristolactam (<bold>92</bold>), an aristolactam alkaloid, as well as (-)-anonaine (<bold>55</bold>). Compounds <bold>92</bold> and <bold>55</bold> are active against a chloroquine-sensitive <italic>P. falciparum</italic> line (3D7) with IC<sub>50</sub> values of 9.0 and 7.0 <italic>μ</italic>M, respectively. The novel natural products (<bold>90</bold> and <bold>91</bold>) display no <italic>in vitro</italic> antiparasitic activity at 50 <italic>μ</italic>M. Data from the study suggested that 3-methoxy substituent moderately reduces biological function. Also methylation of the nitrogen and demethoxylation at C-8 in the aristolactam skeleton (compound <bold>92</bold>) are important for <italic>P. falciparum</italic> growth inhibition [<xref rid="B60" ref-type="bibr">60</xref>].</p></sec><sec id="sec1.12"><title>1.12. Acridone Alkaloids</title><p>The root bark of <italic>Zanthoxylum simullans</italic> Hance afforded five known acridone alkaloids, together with other compounds. Their antimalarial activity was tested against two different strains of the parasite <italic>P. falciparum</italic>, 3D7 and Dd2. Normelicopidine (<bold>93</bold>) is the most active against Dd2 with IC<sub>50</sub> value of 18.9 ug/mL [<xref rid="B61" ref-type="bibr">61</xref>].</p></sec><sec id="sec1.13"><title>1.13. Macrocyclic Alkaloids</title><p>The macrocyclic dilactone alkaloid, carpaine (<bold>94</bold>), was isolated from <italic>Carica papaya</italic> L. leaf. The compound (<bold>94)</bold> was screened against <italic>Plasmodium falciparum</italic> 3D7 and Dd2 strains. The cytotoxicity was evaluated against NL20 cells. The compound exhibits good activity against both strains of <italic>P. falciparum</italic>, 3D7 and Dd2, with IC<sub>50</sub> values of 4.21 <italic>μ</italic>M and 4.57 <italic>μ</italic>M, respectively, and high selectivity for the parasite and was nontoxic to healthy uninfected human red blood cells [<xref rid="B62" ref-type="bibr">62</xref>]. The effects of <bold>94</bold> may be related to its macrocyclic dilactone structure, a possible cation chelating structure.</p><p>The chemical structures of the quinoline, pyridocoumarin, aristolactam, acridone, and macrocytic alkaloids are shown in <xref ref-type="fig" rid="fig11">Figure 11</xref>. <xref rid="tab1" ref-type="table"> Table 1</xref> presents the summary of the alkaloids and their antimalarial activity.</p></sec></sec><sec id="sec2"><title>2. Conclusion</title><p>In the present review, attempt has been made to document the alkaloidal compounds isolated from medicinal plants and/or investigated recently for their antimalarial property. They belong to a great structural diversity including terpenoide, steroid, indole, phenanthroindolizine, isoquinoline, benzylisoquinoline, hasubanane, naphthoisoquinoline, aporphine, morphinandienone, protoberberine, Amaryllidaceae, cyclopeptide, quinoline, pyridocoumarin, acridone, and macrocyclic alkaloids. Many of the compounds with interesting antimalarial property were reported for the first time within this period and they present an array of potential lead compounds towards development of novel antimalarial drugs. Their antiplasmodial and cytotoxicity data were presented. Structure activity relationships were discussed where possible.</p><p>Particularly, the most interesting of the newly isolated compounds include the cassane-type diterpene alkaloids, caesalminines A (<bold>1</bold>) and caesalminines B (<bold>2</bold>), and the bisindole alkaloid, strychnobaillonine (<bold>19</bold>). Some other known compounds, including the isoquinolines, cycleanine (<bold>25</bold>), and 10-demethylxylopinine (<bold>26</bold>), were also reported to show strong antimalarial property with low IC<sub>50</sub> values. However, some of the compounds have relatively high cytotoxicity profile, while some have not been investigated for their toxicity profile. Another observation is that majority of the study of the antimalarial activity has been based on <italic>in vitro</italic> studies, while <italic>in vivo</italic> studies are quite rare.</p><p>Given the above, it is suggested that further structural modifications and structure-activity relationship study should be done on the promising compounds. The identified alkaloids with promising antimalarial activity should serve as lead compounds for drug design to obtain compounds with improved efficacy and lower toxicity. They should also be subjected to toxicity and <italic>in vivo</italic> efficacy studies. Additionally, the mode of action of the promising compounds should be explored. It is hoped that the outcome of the present review will spur further research into the structural modification and/or development of the promising compounds as novel antimalarial drugs.</p></sec></body><back><sec sec-type="COI-statement"><title>Conflicts of Interest</title><p>The author declares no conflicts of interest.</p></sec><ref-list><ref id="B1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ashok</surname><given-names>P.</given-names></name><name><surname>Ganguly</surname><given-names>S.</given-names></name><name><surname>Murugesan</surname><given-names>S.</given-names></name></person-group><article-title>Review on <italic>in-vitro</italic> anti-malarial activity of natural <italic>β</italic>-carboline alkaloid</article-title><source><italic toggle="yes">Mini-Reviews in Medicinal Chemistry</italic></source><year>2013</year><volume>13</volume><issue>12</issue><fpage>1778</fpage><lpage>1791</lpage><pub-id pub-id-type="doi">10.2174/1389557511313120008</pub-id><pub-id pub-id-type="other">2-s2.0-84888042398</pub-id><pub-id pub-id-type="pmid">24059727</pub-id></element-citation></ref><ref id="B2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kaur</surname><given-names>K.</given-names></name><name><surname>Jain</surname><given-names>M.</given-names></name><name><surname>Khan</surname><given-names>S. I.</given-names></name><etal></etal></person-group><article-title>Synthesis, antiprotozoal, antimicrobial, <italic>β</italic>- hematin inhibition, cytotoxicity and methemoglobin (MetHb) formation activities of bis(8-aminoquinolines)</article-title><source><italic toggle="yes">Bioorganic & Medicinal Chemistry</italic></source><year>2011</year><volume>19</volume><issue>1</issue><fpage>197</fpage><lpage>210</lpage><pub-id pub-id-type="doi">10.1016/j.bmc.2010.11.036</pub-id><pub-id pub-id-type="other">2-s2.0-78650724579</pub-id><pub-id pub-id-type="pmid">21172735</pub-id></element-citation></ref><ref id="B3"><label>3</label><element-citation publication-type="book"><collab>WHO</collab><source><italic toggle="yes">World Malaria Report 2017</italic></source><year>2017</year><publisher-loc>Geneva, Switzerland</publisher-loc><publisher-name>World Health Organization</publisher-name></element-citation></ref><ref id="B4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schlitzer</surname><given-names>M.</given-names></name></person-group><article-title>Antimalarial Drugs—what is in use and what is in the pipeline</article-title><source><italic toggle="yes">Archiv der Pharmazie</italic></source><year>2008</year><volume>341</volume><issue>3</issue><fpage>149</fpage><lpage>163</lpage><pub-id pub-id-type="doi">10.1002/ardp.200700184</pub-id><pub-id pub-id-type="other">2-s2.0-44349176702</pub-id><pub-id pub-id-type="pmid">18297679</pub-id></element-citation></ref><ref id="B5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wiesner</surname><given-names>J.</given-names></name><name><surname>Ortmann</surname><given-names>R.</given-names></name><name><surname>Jomaa</surname><given-names>H.</given-names></name><name><surname>Schlitzer</surname><given-names>M.</given-names></name></person-group><article-title>New antimalarial drugs</article-title><source><italic toggle="yes">Angewandte Chemie International Edition</italic></source><year>2003</year><volume>42</volume><issue>43</issue><fpage>5274</fpage><lpage>5293</lpage><pub-id pub-id-type="doi">10.1002/anie.200200569</pub-id><pub-id pub-id-type="other">2-s2.0-0344875966</pub-id><pub-id pub-id-type="pmid">14613157</pub-id></element-citation></ref><ref id="B6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Onori</surname><given-names>E.</given-names></name></person-group><article-title>The problem of <italic>Plasmodium falciparum</italic> drug resistance in Africa south of the Sahara</article-title><source><italic toggle="yes">Bulletin of the World Health Organization</italic></source><year>1984</year><volume>62</volume><fpage>55</fpage><lpage>62</lpage><pub-id pub-id-type="pmid">6397277</pub-id></element-citation></ref><ref id="B7"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kain</surname><given-names>K. C.</given-names></name><name><surname>Shanks</surname><given-names>G. D.</given-names></name><name><surname>Keystone</surname><given-names>J. S.</given-names></name></person-group><article-title>Malaria chemoprophylaxis in the age of drug resistance. I. currently recommended drug regimens</article-title><source><italic toggle="yes">Clinical Infectious Diseases</italic></source><year>2001</year><volume>33</volume><issue>2</issue><fpage>226</fpage><lpage>234</lpage><pub-id pub-id-type="doi">10.1086/321817</pub-id><pub-id pub-id-type="other">2-s2.0-0035879522</pub-id><pub-id pub-id-type="pmid">11418883</pub-id></element-citation></ref><ref id="B8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mugittu</surname><given-names>K.</given-names></name><name><surname>Genton</surname><given-names>B.</given-names></name><name><surname>Mshinda</surname><given-names>H.</given-names></name><name><surname>Beck</surname><given-names>H. P.</given-names></name></person-group><article-title>Molecular monitoring of <italic>Plasmodium falciparum</italic> resistance to artemisinin in Tanzania</article-title><source><italic toggle="yes">Malaria Journal</italic></source><year>2006</year><volume>5</volume><issue>1</issue><pub-id pub-id-type="doi">10.1186/1475-2875-5-126</pub-id><pub-id pub-id-type="other">2-s2.0-33846600057</pub-id></element-citation></ref><ref id="B9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Anthony</surname><given-names>M. P.</given-names></name><name><surname>Burrows</surname><given-names>J. N.</given-names></name><name><surname>Duparc</surname><given-names>S.</given-names></name><name><surname>Moehrle</surname><given-names>J.</given-names></name><name><surname>Wells</surname><given-names>T. N. C.</given-names></name></person-group><article-title>The global pipeline of new medicines for the control and elimination of malaria</article-title><source><italic toggle="yes">Malaria Journal</italic></source><year>2012</year><volume>11</volume><issue>1</issue><fpage>p. 316</fpage><pub-id pub-id-type="doi">10.1186/1475-2875-11-316</pub-id><pub-id pub-id-type="other">2-s2.0-84865832714</pub-id></element-citation></ref><ref id="B10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ginsburg</surname><given-names>H.</given-names></name><name><surname>Deharo</surname><given-names>E.</given-names></name></person-group><article-title>A call for using natural compounds in the development of new antimalarial treatments an introduction</article-title><source><italic toggle="yes">Malaria Journal</italic></source><year>2011</year><volume>10</volume><issue>S1</issue><pub-id pub-id-type="doi">10.1186/1475-2875-10-s1-s1</pub-id><pub-id pub-id-type="other">2-s2.0-79952763770</pub-id></element-citation></ref><ref id="B11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guantai</surname><given-names>E.</given-names></name><name><surname>Chibale</surname><given-names>K.</given-names></name></person-group><article-title>How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?</article-title><source><italic toggle="yes">Malaria Journal</italic></source><year>2011</year><volume>10</volume><issue>S2</issue><pub-id pub-id-type="doi">10.1186/1475-2875-10-s1-s2</pub-id><pub-id pub-id-type="other">2-s2.0-79952765894</pub-id></element-citation></ref><ref id="B12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cruz</surname><given-names>L. R.</given-names></name><name><surname>Spangenberg</surname><given-names>T.</given-names></name><name><surname>Lacerda</surname><given-names>M. V. G.</given-names></name><name><surname>Wells</surname><given-names>T. N. C.</given-names></name></person-group><article-title>Malaria in South America: a drug discovery perspective</article-title><source><italic toggle="yes">Malaria Journal</italic></source><year>2013</year><volume>12</volume><issue>1</issue><pub-id pub-id-type="doi">10.1186/1475-2875-12-168</pub-id><pub-id pub-id-type="other">2-s2.0-84878007734</pub-id></element-citation></ref><ref id="B13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Onguéné</surname><given-names>P. A.</given-names></name><name><surname>Ntie-Kang</surname><given-names>F.</given-names></name><name><surname>Lifongo</surname><given-names>L. L.</given-names></name><name><surname>Ndom</surname><given-names>J. C.</given-names></name><name><surname>Sipp</surname><given-names>W.</given-names></name><name><surname>Mbaze</surname><given-names>L. M.</given-names></name></person-group><article-title>The potential of anti-malarial compounds derived from African medicinal plants. Part I: a pharmacological evaluation of alkaloids and terpenoids</article-title><source><italic toggle="yes">Malaria Journal</italic></source><year>2013</year><volume>2</volume><issue>1</issue><fpage>p. 449</fpage><pub-id pub-id-type="doi">10.1186/1475-2875-12-449</pub-id><pub-id pub-id-type="other">2-s2.0-84889963098</pub-id></element-citation></ref><ref id="B14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wells</surname><given-names>T. N. C.</given-names></name></person-group><article-title>Natural products as starting points for future anti-malarial therapies: going back to our roots?</article-title><source><italic toggle="yes">Malaria Journal</italic></source><year>2011</year><volume>10</volume><issue>S1</issue><pub-id pub-id-type="doi">10.1186/1475-2875-10-s1-s3</pub-id><pub-id pub-id-type="other">2-s2.0-79952741062</pub-id></element-citation></ref><ref id="B15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kaur</surname><given-names>R.</given-names></name><name><surname>Arora</surname><given-names>S.</given-names></name></person-group><article-title>Alkaloids-important therapeutic secondary metabolites of plant origin</article-title><source><italic toggle="yes">Journal of Critical Reviews</italic></source><year>2015</year><volume>2</volume><issue>3</issue><fpage>1</fpage><lpage>8</lpage></element-citation></ref><ref id="B16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ayuko</surname><given-names>T. A. A.</given-names></name><name><surname>Njau</surname><given-names>R. N.</given-names></name><name><surname>Cornelius</surname><given-names>W.</given-names></name><name><surname>Leah</surname><given-names>N.</given-names></name><name><surname>Ndiege</surname><given-names>I. O.</given-names></name></person-group><article-title>In vitro antiplasmodial activity and toxicity assessment of plant extracts used in traditional malaria therapy in the Lake Victoria region</article-title><source><italic toggle="yes">Memórias Do Instituto Oswaldo Cruz</italic></source><year>2009</year><volume>104</volume><issue>5</issue><fpage>689</fpage><lpage>694</lpage><pub-id pub-id-type="doi">10.1590/s0074-02762009000500004</pub-id><pub-id pub-id-type="other">2-s2.0-70349656494</pub-id><pub-id pub-id-type="pmid">19820826</pub-id></element-citation></ref><ref id="B17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bero</surname><given-names>J.</given-names></name><name><surname>Frédérich</surname><given-names>M.</given-names></name><name><surname>Quetin-Leclercq</surname><given-names>J.</given-names></name></person-group><article-title>Antimalarial compounds isolated from plants used in traditional medicine</article-title><source><italic toggle="yes">Journal of Pharmacy and Pharmacology</italic></source><year>2009</year><volume>61</volume><issue>11</issue><fpage>1401</fpage><lpage>1433</lpage><pub-id pub-id-type="doi">10.1211/jpp.61.11.0001</pub-id><pub-id pub-id-type="other">2-s2.0-75749128268</pub-id><pub-id pub-id-type="pmid">19903367</pub-id></element-citation></ref><ref id="B18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bhatnagar</surname><given-names>S.</given-names></name><name><surname>Das</surname><given-names>P.</given-names></name></person-group><article-title>Antimalarial activity in tropical plants: a review</article-title><source><italic toggle="yes">Journal of Herbs, Spices & Medicinal Plants</italic></source><year>2007</year><volume>13</volume><issue>1</issue><fpage>103</fpage><lpage>132</lpage><pub-id pub-id-type="doi">10.1300/j044v13n01_09</pub-id><pub-id pub-id-type="other">2-s2.0-36448988976</pub-id></element-citation></ref><ref id="B19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ntie-Kang</surname><given-names>F.</given-names></name><name><surname>Lifongo</surname><given-names>L. L.</given-names></name><name><surname>Mbaze</surname><given-names>L. M.</given-names></name><etal></etal></person-group><article-title>Cameroonian medicinal plants: a bioactivity versus ethnobotanical survey and chemotaxonomic classification</article-title><source><italic toggle="yes">BMC Complementary and Alternative Medicine</italic></source><year>2013</year><volume>13</volume><issue>1</issue><pub-id pub-id-type="doi">10.1186/1472-6882-13-147</pub-id><pub-id pub-id-type="other">2-s2.0-84879454872</pub-id></element-citation></ref><ref id="B20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schwikkard</surname><given-names>S.</given-names></name><name><surname>Van Heerden</surname><given-names>F. R.</given-names></name></person-group><article-title>Antimalarial activity of plant metabolites</article-title><source><italic toggle="yes">Natural Product Reports</italic></source><year>2002</year><volume>19</volume><issue>6</issue><fpage>675</fpage><lpage>692</lpage><pub-id pub-id-type="doi">10.1039/b008980j</pub-id><pub-id pub-id-type="other">2-s2.0-0036919713</pub-id><pub-id pub-id-type="pmid">12521264</pub-id></element-citation></ref><ref id="B21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ma</surname><given-names>G.</given-names></name><name><surname>Sun</surname><given-names>Z.</given-names></name><name><surname>Sun</surname><given-names>Z.</given-names></name><etal></etal></person-group><article-title>Antimalarial diterpene alkaloids from the seeds of <italic>Caesalpinia minax</italic></article-title><source><italic toggle="yes">Fitoterapia</italic></source><year>2014</year><volume>95</volume><fpage>234</fpage><lpage>239</lpage><pub-id pub-id-type="doi">10.1016/j.fitote.2014.04.001</pub-id><pub-id pub-id-type="other">2-s2.0-84899494471</pub-id><pub-id pub-id-type="pmid">24727083</pub-id></element-citation></ref><ref id="B22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kouam</surname><given-names>S. F.</given-names></name><name><surname>Ngouonpe</surname><given-names>A. W.</given-names></name><name><surname>Lamshöft</surname><given-names>M.</given-names></name><etal></etal></person-group><article-title>Indolosesquiterpene alkaloids from the Cameroonian medicinal plant <italic>Polyalthia oliveri</italic> (Annonaceae)</article-title><source><italic toggle="yes">Phytochemistry</italic></source><year>2014</year><volume>105</volume><fpage>52</fpage><lpage>59</lpage><pub-id pub-id-type="doi">10.1016/j.phytochem.2014.06.015</pub-id><pub-id pub-id-type="other">2-s2.0-84905441652</pub-id><pub-id pub-id-type="pmid">25039009</pub-id></element-citation></ref><ref id="B23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jonville</surname><given-names>M.-C.</given-names></name><name><surname>Dive</surname><given-names>G.</given-names></name><name><surname>Angenot</surname><given-names>L.</given-names></name><etal></etal></person-group><article-title>Dimeric bisindole alkaloids from the stem bark of strychnos nux-vomica L</article-title><source><italic toggle="yes">Phytochemistry</italic></source><year>2013</year><volume>87</volume><fpage>157</fpage><lpage>163</lpage><pub-id pub-id-type="doi">10.1016/j.phytochem.2012.11.002</pub-id><pub-id pub-id-type="other">2-s2.0-84872802455</pub-id><pub-id pub-id-type="pmid">23219610</pub-id></element-citation></ref><ref id="B24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Muganza</surname><given-names>D. M.</given-names></name><name><surname>Fruth</surname><given-names>B.</given-names></name><name><surname>Nzunzu</surname><given-names>J. L.</given-names></name><etal></etal></person-group><article-title><italic>In vitro</italic> antiprotozoal activity and cytotoxicity of extracts and isolated constituents from <italic>Greenwayodendron suaveolens</italic></article-title><source><italic toggle="yes">Journal of Ethnopharmacology</italic></source><year>2016</year><volume>193</volume><fpage>510</fpage><lpage>516</lpage><pub-id pub-id-type="doi">10.1016/j.jep.2016.09.051</pub-id><pub-id pub-id-type="other">2-s2.0-84991735393</pub-id><pub-id pub-id-type="pmid">27693770</pub-id></element-citation></ref><ref id="B25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dua</surname><given-names>V. K.</given-names></name><name><surname>Verma</surname><given-names>G.</given-names></name><name><surname>Singh</surname><given-names>B.</given-names></name><etal></etal></person-group><article-title>Anti-malarial property of steroidal alkaloid conessine isolated from the bark of <italic>Holarrhena antidysenterica</italic></article-title><source><italic toggle="yes">Malaria Journal</italic></source><year>2013</year><volume>12</volume><issue>1</issue><fpage>p. 194</fpage><pub-id pub-id-type="doi">10.1186/1475-2875-12-194</pub-id><pub-id pub-id-type="other">2-s2.0-84878708032</pub-id></element-citation></ref><ref id="B26"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cheenpracha</surname><given-names>S.</given-names></name><name><surname>Boapun</surname><given-names>P.</given-names></name><name><surname>Limtharakul Née Ritthiwigrom</surname><given-names>T.</given-names></name><name><surname>Laphookhieo</surname><given-names>S.</given-names></name><name><surname>Pyne</surname><given-names>S. G.</given-names></name></person-group><article-title>Antimalarial and cytotoxic activities of pregnene-type steroidal alkaloids from <italic>Holarrhena pubescens</italic> roots</article-title><source><italic toggle="yes">Natural Product Research</italic></source><year>2019</year><volume>33</volume><issue>6</issue><fpage>782</fpage><lpage>788</lpage><pub-id pub-id-type="doi">10.1080/14786419.2017.1408108</pub-id><pub-id pub-id-type="other">2-s2.0-85034848291</pub-id><pub-id pub-id-type="pmid">29172699</pub-id></element-citation></ref><ref id="B27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pan</surname><given-names>L.</given-names></name><name><surname>Muñoz Acuña</surname><given-names>U.</given-names></name><name><surname>Chai</surname><given-names>H.</given-names></name><etal></etal></person-group><article-title>New bioactive lupane triterpene coumaroyl esters isolated from <italic>Buxus cochinchinensis</italic></article-title><source><italic toggle="yes">Planta Medica</italic></source><year>2015</year><volume>81</volume><issue>12-13</issue><fpage>1133</fpage><lpage>1140</lpage><pub-id pub-id-type="doi">10.1055/s-0035-1546118</pub-id><pub-id pub-id-type="other">2-s2.0-84940467206</pub-id><pub-id pub-id-type="pmid">26132853</pub-id></element-citation></ref><ref id="B28"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cheenpracha</surname><given-names>S.</given-names></name><name><surname>Ritthiwigrom</surname><given-names>T.</given-names></name><name><surname>Laphookhieo</surname><given-names>S.</given-names></name></person-group><article-title>Alstoniaphyllines A-C, unusual nitrogenous derivatives from the bark of <italic>Alstonia macrophylla</italic></article-title><source><italic toggle="yes">Journal of Natural Products</italic></source><year>2013</year><volume>76</volume><issue>4</issue><fpage>723</fpage><lpage>726</lpage><pub-id pub-id-type="doi">10.1021/np3006937</pub-id><pub-id pub-id-type="other">2-s2.0-84876930059</pub-id><pub-id pub-id-type="pmid">23806072</pub-id></element-citation></ref><ref id="B29"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>dos Santos Torres</surname><given-names>Z.</given-names></name><name><surname>Silveira</surname><given-names>E.</given-names></name><name><surname>Rocha e Silva</surname><given-names>L.</given-names></name><etal></etal></person-group><article-title>Chemical composition of <italic>Aspidosperma ulei</italic> Markgr. and antiplasmodial activity of selected indole alkaloids</article-title><source><italic toggle="yes">Molecules</italic></source><year>2013</year><volume>18</volume><issue>6</issue><fpage>6281</fpage><lpage>6297</lpage><pub-id pub-id-type="doi">10.3390/molecules18066281</pub-id><pub-id pub-id-type="other">2-s2.0-84879678652</pub-id><pub-id pub-id-type="pmid">23760029</pub-id></element-citation></ref><ref id="B30"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tchinda</surname><given-names>A. T.</given-names></name><name><surname>Jansen</surname><given-names>O.</given-names></name><name><surname>Nyemb</surname><given-names>J.-N.</given-names></name><etal></etal></person-group><article-title>Strychnobaillonine, an unsymmetrical bisindole alkaloid with an unprecedented skeleton from <italic>Strychnos icaja</italic> roots</article-title><source><italic toggle="yes">Journal of Natural Products</italic></source><year>2014</year><volume>77</volume><issue>4</issue><fpage>1078</fpage><lpage>1082</lpage><pub-id pub-id-type="doi">10.1021/np400908u</pub-id><pub-id pub-id-type="other">2-s2.0-84899506969</pub-id><pub-id pub-id-type="pmid">24593048</pub-id></element-citation></ref><ref id="B31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amelia</surname><given-names>P.</given-names></name><name><surname>Nugroho</surname><given-names>A. E.</given-names></name><name><surname>Hirasawa</surname><given-names>Y.</given-names></name><etal></etal></person-group><article-title>Two new sarpagine-type indole alkaloids and antimalarial activity of 16-demethoxycarbonylvoacamine from <italic>Tabernaemontana macrocarpa</italic> Jack</article-title><source><italic toggle="yes">Journal of Natural Medicines</italic></source><year>2019</year><volume>73</volume><issue>4</issue><fpage>820</fpage><lpage>825</lpage><pub-id pub-id-type="doi">10.1007/s11418-019-01317-4</pub-id><pub-id pub-id-type="other">2-s2.0-85066829739</pub-id><pub-id pub-id-type="pmid">31140017</pub-id></element-citation></ref><ref id="B32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kubo</surname><given-names>M.</given-names></name><name><surname>Yatsuzuka</surname><given-names>W.</given-names></name><name><surname>Matsushima</surname><given-names>S.</given-names></name><etal></etal></person-group><article-title>Antimalarial phenanthroindolizine alkaloids from <italic>Ficus septica</italic></article-title><source><italic toggle="yes">Chemical and Pharmaceutical Bulletin</italic></source><year>2016</year><volume>64</volume><issue>7</issue><fpage>957</fpage><lpage>960</lpage><pub-id pub-id-type="doi">10.1248/cpb.c16-00181</pub-id><pub-id pub-id-type="other">2-s2.0-84977277772</pub-id><pub-id pub-id-type="pmid">27373653</pub-id></element-citation></ref><ref id="B33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fadaeinasab</surname><given-names>M.</given-names></name><name><surname>Taha</surname><given-names>H.</given-names></name><name><surname>Fauzi</surname><given-names>P. N.</given-names></name><name><surname>Ali</surname><given-names>H. M.</given-names></name><name><surname>Widyawaruyanti</surname><given-names>A.</given-names></name></person-group><article-title>Anti-malarial activity of isoquinoline alkaloids from the stem bark of <italic>Actinodaphne macrophylla</italic></article-title><source><italic toggle="yes">Natural Product Communications</italic></source><year>2015</year><volume>10</volume><issue>9</issue><fpage>1541</fpage><lpage>1542</lpage><pub-id pub-id-type="doi">10.1177/1934578x1501000913</pub-id><pub-id pub-id-type="pmid">26594753</pub-id></element-citation></ref><ref id="B34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nasrullah</surname><given-names>A.</given-names></name><name><surname>Zahari</surname><given-names>A.</given-names></name><name><surname>Mohamad</surname><given-names>J.</given-names></name><name><surname>Awang</surname><given-names>K.</given-names></name></person-group><article-title>Antiplasmodial alkaloids from the bark of <italic>Cryptocarya nigra</italic> (Lauraceae)</article-title><source><italic toggle="yes">Molecules</italic></source><year>2013</year><volume>18</volume><issue>7</issue><fpage>8009</fpage><lpage>8017</lpage><pub-id pub-id-type="doi">10.3390/molecules18078009</pub-id><pub-id pub-id-type="other">2-s2.0-84880838665</pub-id><pub-id pub-id-type="pmid">23884132</pub-id></element-citation></ref><ref id="B35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Malebo</surname><given-names>H. M.</given-names></name><name><surname>Wenzler</surname><given-names>T.</given-names></name><name><surname>Cal</surname><given-names>M.</given-names></name><etal></etal></person-group><article-title>Anti-protozoal activity of aporphine and protoberberine alkaloids from <italic>Annickia kummeriae</italic> (Engl. & Diels) Setten & Maas (Annonaceae)</article-title><source><italic toggle="yes">BMC Complementary and Alternative Medicine</italic></source><year>2013</year><volume>13</volume><issue>1</issue><pub-id pub-id-type="doi">10.1186/1472-6882-13-48</pub-id><pub-id pub-id-type="other">2-s2.0-84874263285</pub-id></element-citation></ref><ref id="B36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goodman</surname><given-names>C. D.</given-names></name><name><surname>Austarheim</surname><given-names>I.</given-names></name><name><surname>Mollard</surname><given-names>V.</given-names></name><etal></etal></person-group><article-title>Natural products from <italic>Zanthoxylum heitzii</italic> with potent activity against the malaria parasite</article-title><source><italic toggle="yes">Malaria Journal</italic></source><year>2016</year><volume>15</volume><issue>1</issue><pub-id pub-id-type="doi">10.1186/s12936-016-1533-x</pub-id><pub-id pub-id-type="other">2-s2.0-84988614853</pub-id></element-citation></ref><ref id="B37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Omole</surname><given-names>R. A.</given-names></name><name><surname>Gathirwa</surname><given-names>J.</given-names></name><name><surname>Akala</surname><given-names>H.</given-names></name><etal></etal></person-group><article-title>Bisbenzylisoquinoline and hasubanane alkaloids from <italic>Stephania abyssinica</italic> (dillon & A. Rich) (menispermeceae)</article-title><source><italic toggle="yes">Phytochemistry</italic></source><year>2014</year><volume>103</volume><fpage>123</fpage><lpage>128</lpage><pub-id pub-id-type="doi">10.1016/j.phytochem.2014.03.026</pub-id><pub-id pub-id-type="other">2-s2.0-84901190382</pub-id><pub-id pub-id-type="pmid">24735823</pub-id></element-citation></ref><ref id="B38"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zahari</surname><given-names>A.</given-names></name><name><surname>Ablat</surname><given-names>A.</given-names></name><name><surname>Sivasothy</surname><given-names>Y.</given-names></name><name><surname>Mohamad</surname><given-names>J.</given-names></name><name><surname>Choudhary</surname><given-names>M. I.</given-names></name><name><surname>Awang</surname><given-names>K.</given-names></name></person-group><article-title><italic>In vitro</italic> antiplasmodial and antioxidant activities of bisbenzylisoquinoline alkaloids from <italic>Alseodaphne corneri</italic> Kosterm</article-title><source><italic toggle="yes">Asian Pacific Journal of Tropical Medicine</italic></source><year>2016</year><volume>9</volume><issue>4</issue><fpage>328</fpage><lpage>332</lpage><pub-id pub-id-type="doi">10.1016/j.apjtm.2016.03.008</pub-id><pub-id pub-id-type="other">2-s2.0-84962921430</pub-id><pub-id pub-id-type="pmid">27086149</pub-id></element-citation></ref><ref id="B39"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>J.</given-names></name><name><surname>Seupel</surname><given-names>R.</given-names></name><name><surname>Feineis</surname><given-names>D.</given-names></name><etal></etal></person-group><article-title>Dioncophyllines C2, D2, and F and related naphthylisoquinoline alkaloids from the Congolese liana <italic>Ancistrocladus ileboensis</italic> with potent activities against <italic>Plasmodium falciparum</italic> and against multiple myeloma and leukemia cell lines</article-title><source><italic toggle="yes">Journal of Natural Products</italic></source><year>2017</year><volume>80</volume><issue>2</issue><fpage>443</fpage><lpage>458</lpage><pub-id pub-id-type="doi">10.1021/acs.jnatprod.6b00967</pub-id><pub-id pub-id-type="other">2-s2.0-85013859843</pub-id><pub-id pub-id-type="pmid">28121440</pub-id></element-citation></ref><ref id="B40"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bringmann</surname><given-names>G.</given-names></name><name><surname>Lombe</surname><given-names>B. K.</given-names></name><name><surname>Steinert</surname><given-names>C.</given-names></name><etal></etal></person-group><article-title>Mbandakamines A and B, unsymmetrically coupled dimeric naphthylisoquinoline alkaloids, from a Congolese Ancistrocladus species</article-title><source><italic toggle="yes">Organic Letters</italic></source><year>2013</year><volume>15</volume><issue>11</issue><fpage>2590</fpage><lpage>2593</lpage><pub-id pub-id-type="doi">10.1021/ol4005883</pub-id><pub-id pub-id-type="other">2-s2.0-84879209522</pub-id><pub-id pub-id-type="pmid">23672531</pub-id></element-citation></ref><ref id="B41"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bringmann</surname><given-names>G.</given-names></name><name><surname>Zhang</surname><given-names>G.</given-names></name><name><surname>Büttner</surname><given-names>T.</given-names></name><etal></etal></person-group><article-title>Jozimine A2: the first dimeric Dioncophyllaceae-type naphthylisoquinoline alkaloid, with three chiral axes and high antiplasmodial activity</article-title><source><italic toggle="yes">Chemistry—A European Journal</italic></source><year>2013</year><volume>19</volume><issue>3</issue><fpage>916</fpage><lpage>923</lpage><pub-id pub-id-type="doi">10.1002/chem.201202755</pub-id><pub-id pub-id-type="other">2-s2.0-84872188454</pub-id></element-citation></ref><ref id="B42"><label>42</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Baghdikian</surname><given-names>B.</given-names></name><name><surname>Mahiou-Leddet</surname><given-names>V.</given-names></name><name><surname>Bory</surname><given-names>S.</given-names></name><etal></etal></person-group><article-title>New antiplasmodial alkaloids from <italic>Stephania rotunda</italic></article-title><source><italic toggle="yes">Journal of Ethnopharmacology</italic></source><year>2013</year><volume>145</volume><issue>1</issue><fpage>381</fpage><lpage>385</lpage><pub-id pub-id-type="doi">10.1016/j.jep.2012.10.052</pub-id><pub-id pub-id-type="other">2-s2.0-84871327585</pub-id><pub-id pub-id-type="pmid">23127648</pub-id></element-citation></ref><ref id="B43"><label>43</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jaidee</surname><given-names>A.</given-names></name><name><surname>Promchai</surname><given-names>T.</given-names></name><name><surname>Trisuwan</surname><given-names>K.</given-names></name><etal></etal></person-group><article-title>Cytotoxic and antimalarial alkaloids from the twigs of <italic>Dasymaschalon obtusipetalum</italic></article-title><source><italic toggle="yes">Natural Product Communications</italic></source><year>2015</year><volume>10</volume><issue>7</issue><fpage>1175</fpage><lpage>1177</lpage><pub-id pub-id-type="doi">10.1177/1934578x1501000709</pub-id><pub-id pub-id-type="pmid">26411003</pub-id></element-citation></ref><ref id="B44"><label>44</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zahari</surname><given-names>A.</given-names></name><name><surname>Cheah</surname><given-names>F.</given-names></name><name><surname>Mohamad</surname><given-names>J.</given-names></name><etal></etal></person-group><article-title>Antiplasmodial and antioxidant isoquinoline alkaloids from <italic>Dehaasia longipedicellata</italic></article-title><source><italic toggle="yes">Planta Medica</italic></source><year>2014</year><volume>80</volume><issue>7</issue><fpage>599</fpage><lpage>603</lpage><pub-id pub-id-type="doi">10.1055/s-0034-1368349</pub-id><pub-id pub-id-type="other">2-s2.0-84901188613</pub-id><pub-id pub-id-type="pmid">24723007</pub-id></element-citation></ref><ref id="B45"><label>45</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gontijo</surname><given-names>D. C.</given-names></name><name><surname>Brandão</surname><given-names>G. C.</given-names></name><name><surname>Nascimento</surname><given-names>M. F. A. D.</given-names></name><name><surname>Oliveira</surname><given-names>A. B. D.</given-names></name></person-group><article-title>Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and dereplication of <italic>Xylopia sericea</italic> leaves ethanol extract by UPLC-DAD-ESI-MS/MS</article-title><source><italic toggle="yes">Journal of Pharmacy and Pharmacology</italic></source><year>2019</year><volume>71</volume><issue>2</issue><fpage>260</fpage><lpage>269</lpage><pub-id pub-id-type="doi">10.1111/jphp.13029</pub-id><pub-id pub-id-type="other">2-s2.0-85054631462</pub-id><pub-id pub-id-type="pmid">30303245</pub-id></element-citation></ref><ref id="B46"><label>46</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Omar</surname><given-names>H.</given-names></name><name><surname>Fadaeinasa</surname><given-names>M.</given-names></name><name><surname>Taha</surname><given-names>H.</given-names></name><name><surname>Widyawaruyanti</surname><given-names>A.</given-names></name><name><surname>Nafiah</surname><given-names>M. A.</given-names></name><name><surname>Rachmatiah</surname><given-names>T.</given-names></name></person-group><article-title>Aporphine alkaloids with <italic>in vitro</italic> antiplasmodial activity from the leaves of <italic>Phoebe tavoyana</italic></article-title><source><italic toggle="yes">Journal of Asian Natural Product Research</italic></source><year>2019</year><volume>22</volume><issue>1</issue><fpage>52</fpage><lpage>60</lpage><pub-id pub-id-type="doi">10.1080/10286020.2018.1553958</pub-id><pub-id pub-id-type="other">2-s2.0-85063189000</pub-id></element-citation></ref><ref id="B47"><label>47</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wangchuk</surname><given-names>P.</given-names></name><name><surname>Keller</surname><given-names>P. A.</given-names></name><name><surname>Pyne</surname><given-names>S. G.</given-names></name><etal></etal></person-group><article-title>A new protoberberine alkaloid from <italic>Meconopsis simplicifolia</italic> (D. Don) Walpers with potent antimalarial activity against a multidrug resistant <italic>Plasmodium falciparum strain</italic></article-title><source><italic toggle="yes">Journal of Ethnopharmacology</italic></source><year>2013</year><volume>150</volume><issue>3</issue><fpage>953</fpage><lpage>959</lpage><pub-id pub-id-type="doi">10.1016/j.jep.2013.09.052</pub-id><pub-id pub-id-type="other">2-s2.0-84889091616</pub-id><pub-id pub-id-type="pmid">24120516</pub-id></element-citation></ref><ref id="B48"><label>48</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lang</surname><given-names>L.</given-names></name><name><surname>Hu</surname><given-names>Q.</given-names></name><name><surname>Wang</surname><given-names>J.</given-names></name><etal></etal></person-group><article-title>Coptisine, a natural alkaloid from <italic>Coptidis rhizoma</italic>, inhibits <italic>Plasmodium falciparum</italic> dihydroorotate dehydrogenase</article-title><source><italic toggle="yes">Chemical Biology & Drug Design</italic></source><year>2018</year><volume>92</volume><issue>1</issue><fpage>1324</fpage><lpage>1332</lpage><pub-id pub-id-type="doi">10.1111/cbdd.13197</pub-id><pub-id pub-id-type="other">2-s2.0-85046725193</pub-id><pub-id pub-id-type="pmid">29582555</pub-id></element-citation></ref><ref id="B49"><label>49</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Promchai</surname><given-names>T.</given-names></name><name><surname>Jaidee</surname><given-names>A.</given-names></name><name><surname>Cheenpracha</surname><given-names>S.</given-names></name><etal></etal></person-group><article-title>Antimalarial oxoprotoberberine alkaloids from the leaves of <italic>Miliusa cuneata</italic></article-title><source><italic toggle="yes">Journal of Natural Products</italic></source><year>2016</year><volume>79</volume><issue>4</issue><fpage>978</fpage><lpage>983</lpage><pub-id pub-id-type="doi">10.1021/acs.jnatprod.5b01054</pub-id><pub-id pub-id-type="other">2-s2.0-84969695160</pub-id><pub-id pub-id-type="pmid">26928423</pub-id></element-citation></ref><ref id="B50"><label>50</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Le</surname><given-names>P. M.</given-names></name><name><surname>Srivastava</surname><given-names>V.</given-names></name><name><surname>Nguyen</surname><given-names>T. T.</given-names></name><etal></etal></person-group><article-title>Stephanine from <italic>Stephania venosa</italic> (Blume) spreng showed effective antiplasmodial and anticancer activities, the latter by inducing apoptosis through the reverse of mitotic exit</article-title><source><italic toggle="yes">Phytotherapy Research</italic></source><year>2017</year><volume>31</volume><issue>9</issue><fpage>1357</fpage><lpage>1368</lpage><pub-id pub-id-type="doi">10.1002/ptr.5861</pub-id><pub-id pub-id-type="other">2-s2.0-85023619817</pub-id><pub-id pub-id-type="pmid">28703314</pub-id></element-citation></ref><ref id="B51"><label>51</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hao</surname><given-names>B.</given-names></name><name><surname>Shen</surname><given-names>S.-F.</given-names></name><name><surname>Zhao</surname><given-names>Q.-J.</given-names></name></person-group><article-title>Cytotoxic and antimalarial amaryllidaceae alkaloids from the bulbs of <italic>Lycoris radiata</italic></article-title><source><italic toggle="yes">Molecules</italic></source><year>2013</year><volume>18</volume><issue>3</issue><fpage>2458</fpage><lpage>2468</lpage><pub-id pub-id-type="doi">10.3390/molecules18032458</pub-id><pub-id pub-id-type="other">2-s2.0-84875619947</pub-id><pub-id pub-id-type="pmid">23439562</pub-id></element-citation></ref><ref id="B52"><label>52</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Presley</surname><given-names>C. C.</given-names></name><name><surname>Krai</surname><given-names>P.</given-names></name><name><surname>Dalal</surname><given-names>S.</given-names></name><etal></etal></person-group><article-title>New potently bioactive alkaloids from <italic>Crinum erubescens</italic></article-title><source><italic toggle="yes">Bioorganic & Medicinal Chemistry</italic></source><year>2016</year><volume>24</volume><issue>21</issue><fpage>5418</fpage><lpage>5422</lpage><pub-id pub-id-type="doi">10.1016/j.bmc.2016.08.058</pub-id><pub-id pub-id-type="other">2-s2.0-84991585583</pub-id><pub-id pub-id-type="pmid">27624525</pub-id></element-citation></ref><ref id="B53"><label>53</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cho</surname><given-names>N.</given-names></name><name><surname>Du</surname><given-names>Y.</given-names></name><name><surname>Valenciano</surname><given-names>A. L.</given-names></name><etal></etal></person-group><article-title>Antiplasmodial alkaloids from bulbs of <italic>Amaryllis belladonna</italic></article-title><source><italic toggle="yes">Bioorganic & Medicinal Chemistry Letters</italic></source><year>2018</year><volume>28</volume><issue>1</issue><fpage>40</fpage><lpage>42</lpage><pub-id pub-id-type="doi">10.1016/j.bmcl.2017.11.021</pub-id><pub-id pub-id-type="other">2-s2.0-85034830487</pub-id><pub-id pub-id-type="pmid">29162457</pub-id></element-citation></ref><ref id="B54"><label>54</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gonring-Salarini</surname><given-names>K. L.</given-names></name><name><surname>Conti</surname><given-names>R.</given-names></name><name><surname>de Andrade</surname><given-names>J. P.</given-names></name><etal></etal></person-group><article-title><italic>In vitro</italic> antiplasmodial activities of alkaloids isolated from roots of <italic>Worsleya procera</italic> (Lem.) Traub (Amaryllidaceae)</article-title><source><italic toggle="yes">Journal of Brazillian Chemical Society</italic></source><year>2019</year><volume>30</volume><issue>8</issue><fpage>1624</fpage><lpage>1633</lpage><pub-id pub-id-type="doi">10.21577/0103-5053.20190061</pub-id><pub-id pub-id-type="other">2-s2.0-85072644277</pub-id></element-citation></ref><ref id="B55"><label>55</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tuenter</surname><given-names>E.</given-names></name><name><surname>Segers</surname><given-names>K.</given-names></name><name><surname>Kang</surname><given-names>K. B.</given-names></name><etal></etal></person-group><article-title>Antiplasmodial activity, cytotoxicity and structure-activity relationship study of cyclopeptide alkaloids</article-title><source><italic toggle="yes">Molecules</italic></source><year>2017</year><volume>22</volume><fpage>p. 224</fpage><pub-id pub-id-type="doi">10.3390/molecules22020224</pub-id><pub-id pub-id-type="other">2-s2.0-85013998421</pub-id></element-citation></ref><ref id="B56"><label>56</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tuenter</surname><given-names>E.</given-names></name><name><surname>Exarchou</surname><given-names>V.</given-names></name><name><surname>Baldé</surname><given-names>A.</given-names></name><etal></etal></person-group><article-title>Cyclopeptide alkaloids from <italic>Hymenocardia acida</italic></article-title><source><italic toggle="yes">Journal of Natural Products</italic></source><year>2016</year><volume>79</volume><issue>7</issue><fpage>1746</fpage><lpage>1751</lpage><pub-id pub-id-type="doi">10.1021/acs.jnatprod.6b00131</pub-id><pub-id pub-id-type="other">2-s2.0-84979520177</pub-id><pub-id pub-id-type="pmid">27351950</pub-id></element-citation></ref><ref id="B57"><label>57</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tuenter</surname><given-names>E.</given-names></name><name><surname>Ahmad</surname><given-names>R.</given-names></name><name><surname>Foubert</surname><given-names>K.</given-names></name><etal></etal></person-group><article-title>Isolation and structure elucidation by LC-DAD-MS and LC-DAD-SPE-NMR of cyclopeptide alkaloids from the roots of <italic>Ziziphus oxyphylla</italic> and evaluation of their antiplasmodial activity</article-title><source><italic toggle="yes">Journal of Natural Products</italic></source><year>2016</year><volume>79</volume><issue>11</issue><fpage>2865</fpage><lpage>2872</lpage><pub-id pub-id-type="doi">10.1021/acs.jnatprod.6b00633</pub-id><pub-id pub-id-type="other">2-s2.0-84999288616</pub-id><pub-id pub-id-type="pmid">27933893</pub-id></element-citation></ref><ref id="B58"><label>58</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kumar</surname><given-names>R.</given-names></name><name><surname>Duffy</surname><given-names>S.</given-names></name><name><surname>Avery</surname><given-names>V. M.</given-names></name><name><surname>Carroll</surname><given-names>A. R.</given-names></name><name><surname>Davis</surname><given-names>R. A.</given-names></name></person-group><article-title>Microthecaline A, a quinoline serrulatane alkaloid from the roots of the Australian desert plant <italic>Eremophila microtheca</italic></article-title><source><italic toggle="yes">Journal of Natural Products</italic></source><year>2018</year><volume>81</volume><issue>4</issue><fpage>1079</fpage><lpage>1083</lpage><pub-id pub-id-type="doi">10.1021/acs.jnatprod.7b00992</pub-id><pub-id pub-id-type="other">2-s2.0-85045994898</pub-id><pub-id pub-id-type="pmid">29533611</pub-id></element-citation></ref><ref id="B59"><label>59</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rasamison</surname><given-names>V. E.</given-names></name><name><surname>Brodie</surname><given-names>P. J.</given-names></name><name><surname>Merino</surname><given-names>E. F.</given-names></name><etal></etal></person-group><article-title>Furoquinoline alkaloids and methoxyflavones from the stem bark of <italic>Melicope madagascariensis</italic> (Baker) T. G. Hartley</article-title><source><italic toggle="yes">Natural Products and Bioprospecting</italic></source><year>2016</year><volume>6</volume><issue>5</issue><fpage>261</fpage><lpage>265</lpage><pub-id pub-id-type="doi">10.1007/s13659-016-0106-6</pub-id><pub-id pub-id-type="other">2-s2.0-85051536386</pub-id><pub-id pub-id-type="pmid">27655634</pub-id></element-citation></ref><ref id="B60"><label>60</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Levrier</surname><given-names>C.</given-names></name><name><surname>Balastrier</surname><given-names>M.</given-names></name><name><surname>Beattie</surname><given-names>K. D.</given-names></name><etal></etal></person-group><article-title>Pyridocoumarin, aristolactam and aporphine alkaloids from the Australian rainforest plant <italic>Goniothalamus australis</italic></article-title><source><italic toggle="yes">Phytochemistry</italic></source><year>2013</year><volume>86</volume><fpage>121</fpage><lpage>126</lpage><pub-id pub-id-type="doi">10.1016/j.phytochem.2012.09.019</pub-id><pub-id pub-id-type="other">2-s2.0-84872049500</pub-id><pub-id pub-id-type="pmid">23158725</pub-id></element-citation></ref><ref id="B61"><label>61</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>C.</given-names></name><name><surname>Wan</surname><given-names>J.</given-names></name><name><surname>Mei</surname><given-names>Z.</given-names></name><name><surname>Xang</surname><given-names>X.</given-names></name></person-group><article-title>Acridone alkaloids with cytotoxic and antimalarial activities from <italic>Zanthoxylum simullans</italic> Hance</article-title><source><italic toggle="yes">Pharmacognosy Magazine</italic></source><year>2014</year><volume>10</volume><issue>37</issue><fpage>73</fpage><lpage>76</lpage><pub-id pub-id-type="doi">10.4103/0973-1296.126669</pub-id><pub-id pub-id-type="other">2-s2.0-84894173638</pub-id><pub-id pub-id-type="pmid">24696549</pub-id></element-citation></ref><ref id="B62"><label>62</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Teng</surname><given-names>W.-C.</given-names></name><name><surname>Chan</surname><given-names>W.</given-names></name><name><surname>Suwanarusk</surname><given-names>R.</given-names></name><etal></etal></person-group><article-title><italic>In vitro</italic> antimalarial evaluations and cytotoxicity investigations of <italic>Carica papaya</italic> leaves and carpaine</article-title><source><italic toggle="yes">Natural Product Communications</italic></source><year>2019</year><volume>14</volume><issue>1</issue><fpage>33</fpage><lpage>36</lpage><pub-id pub-id-type="doi">10.1177/1934578x1901400110</pub-id><pub-id pub-id-type="other">2-s2.0-85063565633</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="fig1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Structures of some antimalarial drugs.</p></caption><graphic xlink:href="ECAM2020-8749083.001"></graphic></fig><fig id="fig2" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Structures of terpenoidal and steroidal alkaloids.</p></caption><graphic xlink:href="ECAM2020-8749083.002"></graphic></fig><fig id="fig3" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Structures of indole and related alkaloids with promising antiplasmodial activity.</p></caption><graphic xlink:href="ECAM2020-8749083.003"></graphic></fig><fig id="fig4" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Structures of isoquinoline alkaloids.</p></caption><graphic xlink:href="ECAM2020-8749083.004"></graphic></fig><fig id="fig5" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Structures of bisbenzylisoquinoline (<bold>40, 41,</bold> and <bold>44</bold>) and hasubanane (<bold>42</bold> and <bold>43</bold>) alkaloids.</p></caption><graphic xlink:href="ECAM2020-8749083.005"></graphic></fig><fig id="fig6" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Structures of naphthylisoquinoline (<bold>45</bold>) and dimeric naphthylisoquinoline (<bold>46</bold>–<bold>48-</bold>) alkaloids.</p></caption><graphic xlink:href="ECAM2020-8749083.006"></graphic></fig><fig id="fig7" orientation="portrait" position="float"><label>Figure 7</label><caption><p>Structures of apophine (<bold>49, 50,</bold> and <bold>52</bold>), isoquinoline (<bold>51</bold>), bisbenzylisoquinoline (<bold>53</bold>), and morphinandienone (<bold>54</bold> and <bold>60</bold>) alkaloids.</p></caption><graphic xlink:href="ECAM2020-8749083.007"></graphic></fig><fig id="fig8" orientation="portrait" position="float"><label>Figure 8</label><caption><p>Structures of protoberberine alkaloids.</p></caption><graphic xlink:href="ECAM2020-8749083.008"></graphic></fig><fig id="fig9" orientation="portrait" position="float"><label>Figure 9</label><caption><p>Structures of Amaryllidaceae alkaloids.</p></caption><graphic xlink:href="ECAM2020-8749083.009"></graphic></fig><fig id="fig10" orientation="portrait" position="float"><label>Figure 10</label><caption><p>Chemical structures of cyclopeptides with antiplasmodial activity.</p></caption><graphic xlink:href="ECAM2020-8749083.010"></graphic></fig><fig id="fig11" orientation="portrait" position="float"><label>Figure 11</label><caption><p>Chemical structures of quinoline (<bold>88</bold> and <bold>89</bold>), pyridocoumarin (<bold>90</bold> and <bold>91</bold>), aristolactam (<bold>92</bold>), acridone (<bold>93</bold>), and macrocytic (<bold>94</bold>) alkaloids with antiplasmodial activity.</p></caption><graphic xlink:href="ECAM2020-8749083.011"></graphic></fig><table-wrap id="tab1" orientation="portrait" position="float"><label>Table 1</label><caption><p>Summary of antimalarial alkaloids derived from plants.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Name</th><th align="center" rowspan="1" colspan="1">Class of alkaloid</th><th align="center" rowspan="1" colspan="1">Source</th><th align="center" rowspan="1" colspan="1">Activity against <italic>P. falciparum</italic></th><th align="center" rowspan="1" colspan="1">Reference</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Two new compounds: caesalminines A (<bold>1</bold>) and caesalminines B (<bold>2</bold>)</td><td align="center" rowspan="1" colspan="1">Cassane-type diterpene alkaloids</td><td align="center" rowspan="1" colspan="1">Seeds of <italic>Caesalpinia minax</italic></td><td align="center" rowspan="1" colspan="1"><italic>In vitro</italic> activity with IC<sub>50</sub>: 0.42 <italic>μ</italic>M (<bold>1</bold>) and 0.79 <italic>μ</italic>M (<bold>2</bold>)</td><td align="center" rowspan="1" colspan="1">[<xref rid="B21" ref-type="bibr">21</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Three new compounds: 8<italic>α</italic>-polyveolinone (<bold>3</bold>), <italic>N</italic>-acetyl-8<italic>α</italic>-polyveolinone (<bold>4</bold>), and <italic>N</italic>-acetyl-polyveoline (<bold>5</bold>)</td><td align="center" rowspan="1" colspan="1">Indolosesquiterpene alkaloids</td><td align="center" rowspan="1" colspan="1">Stem bark of <italic>Polyalthia oliveri</italic></td><td align="center" rowspan="1" colspan="1">Compounds <bold>4</bold> and <bold>5</bold> exhibit moderate activity against NF54 strain, with low cytotoxicity on L6 cell line</td><td align="center" rowspan="1" colspan="1">[<xref rid="B22" ref-type="bibr">22</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Three known alkaloids together with strychnochrysine (<bold>6</bold>)</td><td align="center" rowspan="1" colspan="1">Bisindolomonoterpenic alkaloid</td><td align="center" rowspan="1" colspan="1"><italic>Strychnos nux-vomica</italic> L</td><td align="center" rowspan="1" colspan="1">Compound <bold>7</bold> is the most active with IC<sub>50</sub> 10 <italic>μ</italic>M against D7 strain</td><td align="center" rowspan="1" colspan="1">[<xref rid="B23" ref-type="bibr">23</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Two known alkaloids: polyalthenol (<bold>7</bold>) and <italic>N</italic>-acetyl-polyveoline (<bold>5</bold>), together with other compounds</td><td align="center" rowspan="1" colspan="1">Indolosesquiterpene</td><td align="center" rowspan="1" colspan="1"><italic>Greenwayodendron suaveolens</italic> (Engl. & Diels) Verdc. (syn. <italic>Polyalthia suaveolens</italic> Engl. & Diels)</td><td align="center" rowspan="1" colspan="1">Highest activity was found for compound <bold>5</bold> against K1 strain with IC<sub>50</sub> value of 2.8 <italic>μ</italic>M, SI = 10.9</td><td align="center" rowspan="1" colspan="1">[<xref rid="B24" ref-type="bibr">24</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Conesine (<bold>8</bold>)</td><td align="center" rowspan="1" colspan="1">Steroidal alkaloid</td><td align="center" rowspan="1" colspan="1"><italic>Holarrhena antidysenterica</italic></td><td align="center" rowspan="1" colspan="1"><italic>Shows in vivo acivity against P. berghei</italic><break></break>Also shows <italic>in vitro</italic> activity against <italic>P. falciparum</italic> with IC₅₀ values of 1.9 <italic>μ</italic>g/ml and 1.3 <italic>μ</italic>g/ml in the schizont maturation and pLDH assays, respectively; cytotoxicity IC<sub>50</sub> of 14 <italic>μ</italic>g/ml</td><td align="center" rowspan="1" colspan="1">[<xref rid="B25" ref-type="bibr">25</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">New compound: mokluangin D (<bold>9</bold>) with nine known steroidal alkaloids including irehline (<bold>10</bold>) and mokluangin A (<bold>11</bold>)</td><td align="center" rowspan="1" colspan="1">Pregnene-type alkaloid</td><td align="center" rowspan="1" colspan="1"><italic>Holarrhena pubescens</italic> roots</td><td align="center" rowspan="1" colspan="1">Compounds <bold>10</bold> and <bold>11</bold> show strong activity against K1 strain with IC<sub>50</sub> values of 1.2 and 2.0 <italic>μ</italic>M and weak cytotoxicity against the NCI-H187 cell line</td><td align="center" rowspan="1" colspan="1">[<xref rid="B26" ref-type="bibr">26</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">The known alkaloid, <italic>N</italic>-3-benzoyldihydrocyclomicrophylline F (<bold>12</bold>), together with other compounds</td><td align="center" rowspan="1" colspan="1">Buxus alkaloid (a steroidal alkaloid) (compound <bold>12</bold>)</td><td align="center" rowspan="1" colspan="1"><italic>Buxus cochinchinensis</italic> Pierre ex Gagnep.</td><td align="center" rowspan="1" colspan="1">Compound <bold>12</bold> is active with IC<sub>50</sub> value of 2.07 ± 0.13 <italic>μ</italic>M; it shows cytotoxicity with IC<sub>50</sub> value of 1.9 <italic>μ</italic>M (against HT-29 human carcinoma) and > 20 (against NF-KB)</td><td align="center" rowspan="1" colspan="1">[<xref rid="B27" ref-type="bibr">27</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Three new compounds: alstoniaphyllines A <bold>(13)</bold>, alstoniaphyllines B (<bold>14</bold>), and alstoniaphylline C (<bold>15</bold>), and eight known alkaloids including alstonisine (<bold>16</bold>)</td><td align="center" rowspan="1" colspan="1">Nitrogenous derivatives (<bold>13</bold> and <bold>14</bold>) and indole alkaloid (<bold>15</bold>)</td><td align="center" rowspan="1" colspan="1"><italic>Alstonia macrophylla</italic> bark</td><td align="center" rowspan="1" colspan="1">Compound <bold>16</bold> exhibits activity with IC<sub>50</sub> value of 7.6 <italic>μ</italic>M</td><td align="center" rowspan="1" colspan="1">[<xref rid="B28" ref-type="bibr">28</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">A new compound, 12-hydroxy-<italic>N</italic>-acetyl-21(<italic>N</italic>)-dehydroplumeran-18-oic acid (<bold>17</bold>), and 11 known indole alkaloids including 20-epi-dasycarpidone (<bold>18</bold>)</td><td align="center" rowspan="1" colspan="1">Indole alkaloid</td><td align="center" rowspan="1" colspan="1"><italic>Aspidosperma ulei</italic> Markgr</td><td align="center" rowspan="1" colspan="1">Only compound <bold>18</bold> is active (IC<sub>50</sub> value of 16.7 mM) against K1 strain and shows no toxicity to fibroblasts (IC<sub>50</sub> > 50 mg/mL).</td><td align="center" rowspan="1" colspan="1">[<xref rid="B29" ref-type="bibr">29</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">A new compound: strychnobaillonine (<bold>19</bold>)</td><td align="center" rowspan="1" colspan="1">Bisindole</td><td align="center" rowspan="1" colspan="1">Roots of <italic>Strychnos icaja</italic></td><td align="center" rowspan="1" colspan="1">Shows <italic>in vitro</italic> activity with IC<sub>50</sub> value of 1.1 <italic>μ</italic>M</td><td align="center" rowspan="1" colspan="1">[<xref rid="B30" ref-type="bibr">30</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Two new alkaloids together with five known alkaloids, including 16-demethoxycarbonylvoacamine (<bold>20</bold>)</td><td align="center" rowspan="1" colspan="1">Sarpagine-type indole alkaloids</td><td align="center" rowspan="1" colspan="1">Bark of <italic>Tabernaemontana macrocarpa</italic> Jack</td><td align="center" rowspan="1" colspan="1">Compound <bold>20</bold> shows activity against <italic>P. falciparum</italic> 3D7 and cytotoxic activity against human cell line, HepG2 cells</td><td align="center" rowspan="1" colspan="1">[<xref rid="B31" ref-type="bibr">31</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">New alkaloid, 4a,b-<italic>seco</italic>-dehydroantofine (<bold>21</bold>), and three known alkaloids, dehydrotylophorine (<bold>22</bold>), dehydroantofine (<bold>23</bold>), and tylophoridicine D (<bold>24</bold>)</td><td align="center" rowspan="1" colspan="1">Phenanthroindolizine alkaloids</td><td align="center" rowspan="1" colspan="1">Twigs of <italic>Ficus septica</italic></td><td align="center" rowspan="1" colspan="1">Compound <bold>21</bold> displays moderate activity against the 3D7 strain with IC<sub>50</sub> value of 4.0 <italic>μ</italic>M, whereas the known alkaloids <bold>22</bold>–<bold>24</bold> display strong activity (IC<sub>50</sub> 0.028, 0.42, and 0.058 <italic>μ</italic>M, respectively). The cytotoxicities of the compounds (<bold>21</bold>–<bold>24)</bold> against L929 cells are in the range of 8.2–56 <italic>μ</italic>M, while selectivity index is in the range of 14.0–1964.0</td><td align="center" rowspan="1" colspan="1">[<xref rid="B32" ref-type="bibr">32</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Seven known alkaloids: cycleanine (<bold>25</bold>), 10-demethylxylopinine(<bold>26</bold>), reticuline (<bold>27</bold>), laurotetanine (<bold>28</bold>), bicuculine (<bold>29</bold>), <italic>α</italic>-hydrastine (<bold>30</bold>), and anolobine (<bold>31</bold>)</td><td align="center" rowspan="1" colspan="1">Isoquinoline alkaloids</td><td align="center" rowspan="1" colspan="1">Bark of <italic>Actinodaphne macrophylla</italic></td><td align="center" rowspan="1" colspan="1">They show <italic>in vitro</italic> activity with IC<sub>50</sub> values of 0.08 <italic>μ</italic>M, 0.05 <italic>μ</italic>M, 1.18 <italic>μ</italic>M, 3.11 <italic>μ</italic>M, 0.65 <italic>μ</italic>M, 0.26 <italic>μ</italic>M, and 1.38 <italic>μ</italic>M, respectively, against 3D7 strain</td><td align="center" rowspan="1" colspan="1">[<xref rid="B33" ref-type="bibr">33</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Four known alkaloids: (+)-<italic>N</italic>-methylisococlaurine (<bold>32</bold>), atherosperminine (<bold>33</bold>), 2-hydroxyathersperminine (<bold>34</bold>), and noratherosperminine (<bold>35</bold>)</td><td align="center" rowspan="1" colspan="1">Isoquinoline alkaloids</td><td align="center" rowspan="1" colspan="1">stem bark of <italic>Cryptocarya nigra</italic></td><td align="center" rowspan="1" colspan="1">They display activity with IC<sub>50</sub> values of 5.40, 5.80, and 0.75 <italic>μ</italic>M, respectively, for compounds <bold>32</bold>, <bold>33</bold>, and <bold>34</bold></td><td align="center" rowspan="1" colspan="1">[<xref rid="B34" ref-type="bibr">34</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Four alkaloids including palmatine (<bold>36</bold>)</td><td align="center" rowspan="1" colspan="1">Isoquinoline alkaloids</td><td align="center" rowspan="1" colspan="1">Leaves of <italic>Annickia kummeriae</italic></td><td align="center" rowspan="1" colspan="1">Compound <bold>36</bold> exhibits the highest activity against <italic>P. falciparum</italic> K1 (IC<sub>50</sub> 0.080 ± 0.001 <italic>μ</italic>g/mL, SI = 1154)</td><td align="center" rowspan="1" colspan="1">[<xref rid="B35" ref-type="bibr">35</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Known compounds: dihydronitidine (<bold>37</bold>), pellitorine (<bold>38</bold>), and heitziquinone (<bold>39</bold>)</td><td align="center" rowspan="1" colspan="1">Isoquinoline (dihydronitidine), decadienamide (pellitorine), and benzophenthrathridine (heitziquinone)</td><td align="center" rowspan="1" colspan="1"><italic>Zanthoxylum heitzii</italic> bark</td><td align="center" rowspan="1" colspan="1">Dihydronitidine (<bold>37</bold>) is the most active compound with an IC<sub>50</sub> value of 25 nM, while compounds <bold>38</bold> and <bold>39</bold> have IC<sub>50</sub> values of 9.7 ± 1.6 <italic>μ</italic>M and 8.8 ± 0.5 <italic>μ</italic>M, respectively</td><td align="center" rowspan="1" colspan="1">[<xref rid="B36" ref-type="bibr">36</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Three new alkaloids, (-)-pseudocurine (<bold>40</bold>), (-)-pseudoisocurine (<bold>41</bold>), and (-)-10-oxoaknadinine (<bold>42</bold>)</td><td align="center" rowspan="1" colspan="1">Bisbenzylisoquinoline alkaloids (<bold>40</bold> and <bold>41</bold>) and one hasubanane alkaloid (<bold>42</bold>)</td><td align="center" rowspan="1" colspan="1">Leaf of <italic>Stephania abyssinica</italic></td><td align="center" rowspan="1" colspan="1">They show strong-to-mild activity with IC<sub>50</sub> values ranging from 0.29 ± 0.00 to 1.65 ± 0.03 <italic>μ</italic>g/mL against both chloroquine-susceptible D6 and chloroquine-resistant strains</td><td align="center" rowspan="1" colspan="1">[<xref rid="B37" ref-type="bibr">37</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Six known alkaloids including (+)-laurotetanine (<bold>43</bold>) and (+)-norstephasubine (<bold>44</bold>)</td><td align="center" rowspan="1" colspan="1">Bisbenzylisoquinoline</td><td align="center" rowspan="1" colspan="1"><italic>Alseodaphne corneri</italic></td><td align="center" rowspan="1" colspan="1">Both compounds <bold>43</bold> and <bold>44</bold> show strong activity with IC<sub>50</sub> values of 0.189 and 0.116 <italic>μ</italic>M, respectively, against K1 strain and no cytotoxicity against hTERT-HPNE cell line</td><td align="center" rowspan="1" colspan="1">[<xref rid="B38" ref-type="bibr">38</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">One new dioncophyllaceous alkaloid, dioncophylline F (<bold>45</bold>), and other known alkaloids</td><td align="center" rowspan="1" colspan="1">Naphthylisoquinoline alkaloid (compound <bold>45</bold>)</td><td align="center" rowspan="1" colspan="1"><italic>Ancistrocladus ileboensis</italic></td><td align="center" rowspan="1" colspan="1">Compound <bold>45</bold> together with others shows high and specific activities against <italic>P. falciparum</italic></td><td align="center" rowspan="1" colspan="1">[<xref rid="B39" ref-type="bibr">39</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">New compounds: mbandakamines A (<bold>46</bold>) and B (<bold>47</bold>)</td><td align="center" rowspan="1" colspan="1">Dimeric naphthylisoquinoline alkaloids with an unsymmetrically coupled central biaryl axis</td><td align="center" rowspan="1" colspan="1">Unidentified <italic>Congolese Ancistrocladus</italic> species</td><td align="center" rowspan="1" colspan="1">Compound <bold>46</bold> exhibits good antimalarial activity</td><td align="center" rowspan="1" colspan="1">[<xref rid="B40" ref-type="bibr">40</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">New compound: jozimine A2 (<bold>48</bold>)</td><td align="center" rowspan="1" colspan="1">Dimeric naphthylisoquinoline alkaloid</td><td align="center" rowspan="1" colspan="1">Ancistrocladus species</td><td align="center" rowspan="1" colspan="1">Compound <bold>48</bold> exhibits excellent and specific antiplasmodial activity</td><td align="center" rowspan="1" colspan="1">[<xref rid="B41" ref-type="bibr">41</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">New alkaloid, vireakine (<bold>49</bold>), along with other known alkaloids including stephanine (<bold>50</bold>) and pseudopalmatine (<bold>51</bold>)</td><td align="center" rowspan="1" colspan="1">Aporphine alkaloid (<bold>49</bold>)</td><td align="center" rowspan="1" colspan="1">Tuber of <italic>Stephania rotunda</italic></td><td align="center" rowspan="1" colspan="1">Activity ranged from 1.2 <italic>μ</italic>M to 52.3 <italic>μ</italic>M for all tested compounds; compound <bold>51</bold> (IC<sub>50</sub> = 2.8 <italic>μ</italic>M) shows good selectivity index against W2 chloroquine-resistant strain</td><td align="center" rowspan="1" colspan="1">[<xref rid="B42" ref-type="bibr">42</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">A new alkaloid, obtusipetadione (<bold>52</bold>), and eleven known compounds</td><td align="center" rowspan="1" colspan="1">p-Quinonoid aporphine alkaloid (<bold>52</bold>)</td><td align="center" rowspan="1" colspan="1">Twigs of <italic>Dasymaschalon obtusipetalum</italic></td><td align="center" rowspan="1" colspan="1">Compound <bold>52</bold> is active with IC<sub>50</sub> values of 2.46 ± 0.12 and 1.38 ± 0.99 <italic>μ</italic>g/mL, respectively, for TM4 and K1 strains with no cytotoxicity</td><td align="center" rowspan="1" colspan="1">[<xref rid="B43" ref-type="bibr">43</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Several known alkaloids including (-)-O-O-dimethylgrisabine (<bold>53</bold>) and (-)-milonine (<bold>54)</bold></td><td align="center" rowspan="1" colspan="1">Morphinandienones; aporphines and benzlyisoquinoline</td><td align="center" rowspan="1" colspan="1">Bark of of <italic>Dehaasia longipedicellata</italic></td><td align="center" rowspan="1" colspan="1">They display potent-to-moderate activity with IC<sub>50</sub> values ranging from 0.031 to 30.40 <italic>μ</italic>M. Compounds <bold>53</bold> and <bold>54</bold> are the two most potent compounds, with IC<sub>50</sub> values of 0.031 and 0.097 <italic>μ</italic>M, respectively, against K1 strain. All the compounds show no potency against lung (A549) cancer cells</td><td align="center" rowspan="1" colspan="1">[<xref rid="B44" ref-type="bibr">44</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">A new alkaloid, anonaine (<bold>55</bold>), and other alkaloids</td><td align="center" rowspan="1" colspan="1">Aporphine alkaloids</td><td align="center" rowspan="1" colspan="1"><italic>Xylopia sericea</italic> leaves</td><td align="center" rowspan="1" colspan="1">Compound <bold>55</bold> is active against chloroquine-resistant W2 strain <italic>P. falciparum</italic> (IC<sub>50</sub> 23.2 ± 2.7 <italic>μ</italic>g/mL) and has moderate cytotoxicity against HepG2 cells (SI = 1.6)</td><td align="center" rowspan="1" colspan="1">[<xref rid="B45" ref-type="bibr">45</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">A new alkaloid, tavoyanine A (<bold>56</bold>), and other known alkaloids, roemerine (<bold>57</bold>), laurolitsine (<bold>58</bold>), boldine (<bold>59</bold>), and sebiferine (<bold>60</bold>)</td><td align="center" rowspan="1" colspan="1">Aporphine alkaloids (<bold>56</bold>–<bold>59</bold>) and morphinandienone (<bold>60</bold>)</td><td align="center" rowspan="1" colspan="1">Leaf of <italic>Phoebe tavoyana</italic></td><td align="center" rowspan="1" colspan="1">Compounds <bold>56</bold>–<bold>60</bold> are active against <italic>P. falciparum</italic> with IC<sub>50</sub> values of 0.89, 1.49, 1.65, and 2.76 <italic>μ</italic>g/mL, respectively</td><td align="center" rowspan="1" colspan="1">[<xref rid="B46" ref-type="bibr">46</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">A new alkaloid, simplicifolianine (<bold>61),</bold> together with five known alkaloids</td><td align="center" rowspan="1" colspan="1">Protoberberine-type alkaloid</td><td align="center" rowspan="1" colspan="1">Aerial components of <italic>Meconopsis simplicifolia</italic> (D. Don) Walpers</td><td align="center" rowspan="1" colspan="1">Compound <bold>22</bold> is the most potent against TM4/8.2 and K1CB1 with IC<sub>50</sub> values of 0.78 <italic>μ</italic>g/mL and 1.29 <italic>μ</italic>g/mL, respectively</td><td align="center" rowspan="1" colspan="1">[<xref rid="B47" ref-type="bibr">47</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">A known alkaloid, coptisine (<bold>62</bold>)</td><td align="center" rowspan="1" colspan="1">Protoberberine</td><td align="center" rowspan="1" colspan="1"><italic>Coptidis rhizoma</italic></td><td align="center" rowspan="1" colspan="1">Compound <bold>62</bold> is found to be an inhibitor of PfDHODH with an IC<sub>50</sub> value of 1.83 ± 0.08 <italic>μ</italic>m</td><td align="center" rowspan="1" colspan="1">[<xref rid="B48" ref-type="bibr">48</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Five new alkaloids, miliusacunines A-E (<bold>63</bold>–<bold>67</bold>), along with nine known compounds</td><td align="center" rowspan="1" colspan="1">Oxoprotoberberine alkaloids</td><td align="center" rowspan="1" colspan="1">Leaf and twigs of <italic>Miliusa cuneata</italic></td><td align="center" rowspan="1" colspan="1">Compound <bold>63</bold> shows activity against the TM4 strain (IC<sub>50</sub> 19.3 ± 3.4 <italic>μ</italic>M) and compound <bold>64</bold> shows activity against the K1 strain (IC<sub>50</sub> 10.8 ± 4.1 <italic>μ</italic>M). Both show no cytotoxicity to Vero cells</td><td align="center" rowspan="1" colspan="1">[<xref rid="B49" ref-type="bibr">49</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">One tetrahydroprotoberberine and four aporphine alkaloids including stephanine (<bold>50</bold>)</td><td align="center" rowspan="1" colspan="1">Tetrahydroprotoberberine alkaloid (compound <bold>50</bold>)</td><td align="center" rowspan="1" colspan="1">Tubers of <italic>Stephania venosa</italic> (Blum) Spreng</td><td align="center" rowspan="1" colspan="1">Stephanine (<bold>50</bold>) is the most interesting but is the most cytotoxic with the lowest selectivity index</td><td align="center" rowspan="1" colspan="1">[<xref rid="B50" ref-type="bibr">50</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Five new alkaloids, (+)-5,6-dehydrolycorine (<bold>68</bold>), (+)-3<italic>α</italic>,6<italic>β</italic>-diacetyl-bulbispermine (<bold>69</bold>), (+)-3<italic>α</italic>-hydroxy-6<italic>β</italic>-acetyl-bulbispermine (<bold>70</bold>), (+)-8,9-methylenedioxylhomolycorine-N-oxide (<bold>71</bold>), and 5,6-dihydro-5-methyl-2-hydroxyphenanthridine (<bold>72</bold>), together with other known compounds</td><td align="center" rowspan="1" colspan="1">Amaryllidaceae alkaloids</td><td align="center" rowspan="1" colspan="1">Bulbs of <italic>Lycoris radiata</italic></td><td align="center" rowspan="1" colspan="1">Compound <bold>68</bold> is active with IC<sub>50</sub> values of 2.3 <italic>μ</italic>M for D6 strain and 1.9 <italic>μ</italic>M for W2 strain; compound <bold>68</bold> also shows cytotoxicity against various carcinoma cells with IC<sub>50</sub> values of 9.4–11.6 <italic>μ</italic>M</td><td align="center" rowspan="1" colspan="1">[<xref rid="B51" ref-type="bibr">51</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Three known alkaloids, cripowellin A (<bold>73</bold>), cripowellin B (<bold>74</bold>), and hippadine (<bold>75</bold>), as well as the new compounds cripowellin C (<bold>76</bold>) and D (<bold>77</bold>)</td><td align="center" rowspan="1" colspan="1">Cripowellin alkaloids</td><td align="center" rowspan="1" colspan="1"><italic>Crinum erubescens</italic></td><td align="center" rowspan="1" colspan="1">Compounds <bold>73</bold>, <bold>74, 76</bold>, and <bold>77</bold> are active with IC<sub>50</sub> values of 30 ± 2, 180 ± 20, 26 ± 2, and 260 ± 20 nM, respectively, while <bold>75</bold> is inactive</td><td align="center" rowspan="1" colspan="1">[<xref rid="B52" ref-type="bibr">52</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">New alkaloid, 1,4-dihydroxy-3-methoxy powellan <bold>(78)</bold>, along with the known alkaloids, distichamine (<bold>79)</bold>, 11-O-acetylambelline (<bold>80</bold>), ambelline (<bold>81</bold>), acetylcaranine (<bold>82</bold>), and hippadine (<bold>75</bold>)</td><td align="center" rowspan="1" colspan="1">Crinane (<bold>78</bold>–<bold>81</bold>) and lycorane (<bold>82</bold> and <bold>75</bold>) alkaloids</td><td align="center" rowspan="1" colspan="1"><italic>Amaryllis belladonna</italic> Steud. Bulbs</td><td align="center" rowspan="1" colspan="1">Acetylcaranine (<bold>82</bold>) exhibits strong activity (IC<sub>50</sub> value of 3.3 ± 0.3 <italic>μ</italic>M), while compound <bold>78</bold> is inactive. Compound <bold>82</bold> shows weak inhibition against A2780 ovarian cells with an IC<sub>50</sub> value of 56 ± 1 <italic>μ</italic>M</td><td align="center" rowspan="1" colspan="1">[<xref rid="B53" ref-type="bibr">53</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Lycorine (<bold>83</bold>), along with 14 other alkaloids</td><td align="center" rowspan="1" colspan="1">Amaryllidaceae alkaloids</td><td align="center" rowspan="1" colspan="1"><italic>Worsleya procera</italic> roots</td><td align="center" rowspan="1" colspan="1">Compound <bold>83</bold> was active against both sensitive (3D7) and resistant (K1) <italic>P. falciparum</italic> strains with IC<sub>50</sub> values of 2.5 and 3.1 <italic>μ</italic>M, respectively, and a low cytotoxicity against HepG2 cells</td><td align="center" rowspan="1" colspan="1">[<xref rid="B54" ref-type="bibr">54</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Three new alkaloids, hymenocardinol (<bold>84</bold>), hymenocardine <italic>N</italic>-oxide (<bold>85</bold>), and hymenocardine-H (<bold>86</bold>), and one known alkaloid</td><td align="center" rowspan="1" colspan="1">Cyclopeptide alkaloids</td><td align="center" rowspan="1" colspan="1">Root bark of <italic>Hymenocardia acida</italic></td><td align="center" rowspan="1" colspan="1">All compounds show moderate activity with IC<sub>50</sub> values ranging from 12.2 to 27.9 <italic>μ</italic>M, the most active being compound <bold>85</bold> (IC<sub>50</sub> 12.2 ± 6.6 <italic>μ</italic>M). They are not cytotoxic against MRC-5 cells (IC<sub>50</sub> > 64.0 <italic>μ</italic>M)</td><td align="center" rowspan="1" colspan="1">[<xref rid="B56" ref-type="bibr">56</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Nine alkaloids including <italic>O</italic>-desmethylnummularine-R (<bold>87</bold>)</td><td align="center" rowspan="1" colspan="1">Cyclopeptide alkaloids</td><td align="center" rowspan="1" colspan="1">Roots of <italic>Ziziphus oxyphylla</italic></td><td align="center" rowspan="1" colspan="1">Most promising activity is found for compound <bold>87</bold> with IC<sub>50</sub> value of 3.2 ± 2.6 <italic>μ</italic>M against K1 strain and cytotoxcity (IC<sub>50</sub> value of >64.0 <italic>μ</italic>M) against MRC-5 cells</td><td align="center" rowspan="1" colspan="1">[<xref rid="B57" ref-type="bibr">57</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">A new alkaloid, microthecaline A (<bold>88</bold>)</td><td align="center" rowspan="1" colspan="1">Quinoline-serrulatane</td><td align="center" rowspan="1" colspan="1"><italic>Eremophila microtheca</italic></td><td align="center" rowspan="1" colspan="1">Compound <bold>88</bold> exhibits moderate activity against <italic>P. falciparum</italic> (3D7 strain), with an IC<sub>50</sub> value of 7.7 <italic>μ</italic>M</td><td align="center" rowspan="1" colspan="1">[<xref rid="B58" ref-type="bibr">58</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Seven known alkaloids including 6-methoxy-7-hydroxydictamnine (heliparvifoline) (<bold>89</bold>) and two known compounds</td><td align="center" rowspan="1" colspan="1">Furoquinoline alkaloids</td><td align="center" rowspan="1" colspan="1">Melicope madagascariensis</td><td align="center" rowspan="1" colspan="1">Heliparvifoline (<bold>89</bold>) shows weak antimalarial activity (IC<sub>50</sub> = 35 <italic>μ</italic>M) against Dd2 strain</td><td align="center" rowspan="1" colspan="1">[<xref rid="B59" ref-type="bibr">59</xref>]</td></tr><tr><td align="left" rowspan="1" colspan="1">Two new alkaloids, goniothalines A (<bold>90)</bold> and B (<bold>91</bold>), as well as eight known compounds including sauristolactam (<bold>92</bold>) as well as anonaine (<bold>55)</bold></td><td align="center" rowspan="1" colspan="1">Pyridocoumarin alkaloids</td><td align="center" rowspan="1" colspan="1">Aerial parts of <italic>Goniothalamus australis</italic></td><td align="center" rowspan="1" colspan="1">Sauristolactam (<bold>92</bold>) and (-)-anonaine (<bold>55</bold>) exhibit the most potent activity with IC<sub>50</sub> values of 9 and 7 <italic>μ</italic>M, respectively</td><td align="center" rowspan="1" colspan="1">[<xref rid="B60" ref-type="bibr">60</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Known alkaloids including normelicopine (<bold>93</bold>)</td><td align="center" rowspan="1" colspan="1">Acridone alkaloids</td><td align="center" rowspan="1" colspan="1"><italic>Zanthoxylum simullans</italic> Hance</td><td align="center" rowspan="1" colspan="1">Normelicopidine (<bold>93</bold>) is the most active against Dd2 with IC<sub>50</sub> value of 18.9 <italic>μ</italic>g/mL</td><td align="center" rowspan="1" colspan="1">[<xref rid="B61" ref-type="bibr">61</xref>]</td></tr><tr><td align="left" colspan="5" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">Carpaine (<bold>94</bold>)</td><td align="center" rowspan="1" colspan="1">Macrocyclic alkaloids</td><td align="center" rowspan="1" colspan="1"><italic>Carica papaya</italic> L. leaf</td><td align="center" rowspan="1" colspan="1">The compound is active against both 3D7 and Dd2 strains with IC<sub>50</sub> values of 4.21 <italic>μ</italic>M and 4.57 <italic>μ</italic>M, respectively, and high selectivity for the parasite</td><td align="center" rowspan="1" colspan="1">[<xref rid="B62" ref-type="bibr">62</xref>]</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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