Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances
Identifieur interne : 000054 ( Pmc/Curation ); précédent : 000053; suivant : 000055Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances
Auteurs : Sarvesh K. Paliwal [Inde] ; Ankita Narayan Verma [Inde] ; Shailendra Paliwal [Inde]Source :
- Scientia Pharmaceutica [ 0036-8709 ] ; 2011.
Abstract
Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate
Url:
DOI: 10.3797/scipharm.1012-08
PubMed: 21886894
PubMed Central: 3163371
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances</title><author><name sortKey="Paliwal, Sarvesh K" sort="Paliwal, Sarvesh K" uniqKey="Paliwal S" first="Sarvesh K." last="Paliwal">Sarvesh K. Paliwal</name><affiliation wicri:level="1"><nlm:aff id="af1-scipharm.2011.79.389"> Banasthali University, Distt-Tonk, 304022, Rajasthan, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea> Banasthali University, Distt-Tonk, 304022, Rajasthan</wicri:regionArea></affiliation></author><author><name sortKey="Verma, Ankita Narayan" sort="Verma, Ankita Narayan" uniqKey="Verma A" first="Ankita Narayan" last="Verma">Ankita Narayan Verma</name><affiliation wicri:level="1"><nlm:aff id="af1-scipharm.2011.79.389"> Banasthali University, Distt-Tonk, 304022, Rajasthan, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea> Banasthali University, Distt-Tonk, 304022, Rajasthan</wicri:regionArea></affiliation></author><author><name sortKey="Paliwal, Shailendra" sort="Paliwal, Shailendra" uniqKey="Paliwal S" first="Shailendra" last="Paliwal">Shailendra Paliwal</name><affiliation wicri:level="1"><nlm:aff id="af2-scipharm.2011.79.389"> LLRM medical college, Meerut (U.P.), India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea> LLRM medical college, Meerut (U.P.)</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21886894</idno><idno type="pmc">3163371</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163371</idno><idno type="RBID">PMC:3163371</idno><idno type="doi">10.3797/scipharm.1012-08</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000054</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000054</idno><idno type="wicri:Area/Pmc/Curation">000054</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000054</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances</title><author><name sortKey="Paliwal, Sarvesh K" sort="Paliwal, Sarvesh K" uniqKey="Paliwal S" first="Sarvesh K." last="Paliwal">Sarvesh K. Paliwal</name><affiliation wicri:level="1"><nlm:aff id="af1-scipharm.2011.79.389"> Banasthali University, Distt-Tonk, 304022, Rajasthan, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea> Banasthali University, Distt-Tonk, 304022, Rajasthan</wicri:regionArea></affiliation></author><author><name sortKey="Verma, Ankita Narayan" sort="Verma, Ankita Narayan" uniqKey="Verma A" first="Ankita Narayan" last="Verma">Ankita Narayan Verma</name><affiliation wicri:level="1"><nlm:aff id="af1-scipharm.2011.79.389"> Banasthali University, Distt-Tonk, 304022, Rajasthan, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea> Banasthali University, Distt-Tonk, 304022, Rajasthan</wicri:regionArea></affiliation></author><author><name sortKey="Paliwal, Shailendra" sort="Paliwal, Shailendra" uniqKey="Paliwal S" first="Shailendra" last="Paliwal">Shailendra Paliwal</name><affiliation wicri:level="1"><nlm:aff id="af2-scipharm.2011.79.389"> LLRM medical college, Meerut (U.P.), India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea> LLRM medical college, Meerut (U.P.)</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientia Pharmaceutica</title><idno type="ISSN">0036-8709</idno><idno type="eISSN">2218-0532</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate <italic>Trypanosoma brucei</italic> that mostly occurs in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which have been developed more than 30 years ago, have undesirable toxic side effects and most of them show drug-resistance. Though development of new anti-trypanosomal drugs seems to be a priority area research in this area has lagged far behind. The given review mainly focus upon the recent synthetic and computer based approaches made by various research groups for the development of newer anti-trypanosomal analogues which may have improved efficacy and oral bioavailability than the present ones. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Pharm</journal-id><journal-id journal-id-type="iso-abbrev">Sci Pharm</journal-id><journal-id journal-id-type="publisher-id">Scientia Pharmaceutica</journal-id><journal-title-group><journal-title>Scientia Pharmaceutica</journal-title></journal-title-group><issn pub-type="ppub">0036-8709</issn><issn pub-type="epub">2218-0532</issn><publisher><publisher-name>Österreichische Apotheker-Verlagsgesellschaft</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21886894</article-id><article-id pub-id-type="pmc">3163371</article-id><article-id pub-id-type="doi">10.3797/scipharm.1012-08</article-id><article-id pub-id-type="publisher-id">scipharm.2011.79.389</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Neglected Disease – African Sleeping Sickness: Recent Synthetic and Modeling Advances</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Paliwal</surname><given-names>Sarvesh K.</given-names></name><xref ref-type="aff" rid="af1-scipharm.2011.79.389"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Verma</surname><given-names>Ankita Narayan</given-names></name><xref ref-type="aff" rid="af1-scipharm.2011.79.389"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Paliwal</surname><given-names>Shailendra</given-names></name><xref ref-type="corresp" rid="c1-scipharm.2011.79.389"><sup>*</sup></xref><xref ref-type="aff" rid="af2-scipharm.2011.79.389"><sup>2</sup></xref></contrib></contrib-group><aff id="af1-scipharm.2011.79.389"><label>1</label> Banasthali University, Distt-Tonk, 304022, Rajasthan, India</aff><aff id="af2-scipharm.2011.79.389"><label>2</label> LLRM medical college, Meerut (U.P.), India</aff><author-notes><corresp id="c1-scipharm.2011.79.389"><label>*</label>Corresponding author. E-mails: <email>paliwalsarvesh@yahoo.com</email> or <email>paliwalsarvesh@gmail.com</email> (S. K. Paliwal)</corresp></author-notes><pub-date pub-type="ppub"><season>Jul-Sep</season><year>2011</year></pub-date><pub-date pub-type="epub"><day>10</day><month>5</month><year>2011</year></pub-date><volume>79</volume><issue>3</issue><fpage>389</fpage><lpage>428</lpage><history><date date-type="received"><day>9</day><month>12</month><year>2010</year></date><date date-type="accepted"><day>10</day><month>5</month><year>2011</year></date></history><permissions><copyright-statement>© Paliwal <italic>et al.</italic>; licensee Österreichische Apotheker-Verlagsgesellschaft m. b. H., Vienna, Austria.</copyright-statement><copyright-year>2011</copyright-year><license><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate <italic>Trypanosoma brucei</italic> that mostly occurs in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which have been developed more than 30 years ago, have undesirable toxic side effects and most of them show drug-resistance. Though development of new anti-trypanosomal drugs seems to be a priority area research in this area has lagged far behind. The given review mainly focus upon the recent synthetic and computer based approaches made by various research groups for the development of newer anti-trypanosomal analogues which may have improved efficacy and oral bioavailability than the present ones. The given paper also attempts to investigate the relationship between the various physiochemical parameters and anti-trypanosomal activity that may be helpful in development of potent anti-trypanosomal agents against sleeping sickness.</p></abstract><kwd-group><kwd>Human African Trypanosomiasis (HAT)</kwd><kwd>Computer assisted drug design (CADD)</kwd><kwd>Central nervous system (CNS)</kwd><kwd>Structure-activity relationship (SAR)</kwd><kwd>Trypanothione reductase (TR)</kwd></kwd-group></article-meta></front><floats-group><fig id="f1-scipharm.2011.79.389" position="float"><label>Fig. 1.</label><caption><p>Structure of Pentamidine</p></caption><graphic xlink:href="Scipharm-2011-79-389f1"></graphic></fig><fig id="f2-scipharm.2011.79.389" position="float"><label>Fig. 2.</label><caption><p>Structures of various congeners of pentamidine synthesized by modification in parent pentamidine molecule</p></caption><graphic xlink:href="Scipharm-2011-79-389f2"></graphic></fig><fig id="f3-scipharm.2011.79.389" position="float"><label>Fig. 3.</label><caption><p>Pentamidine analogues with activity better than that of melarsoprol and/or pentamidine</p></caption><graphic xlink:href="Scipharm-2011-79-389f3"></graphic></fig><fig id="f4-scipharm.2011.79.389" position="float"><label>Fig. 4.</label><caption><p>Pyridyl analogues of pentamidine</p></caption><graphic xlink:href="Scipharm-2011-79-389f4"></graphic></fig><fig id="f5-scipharm.2011.79.389" position="float"><label>Fig. 5.</label><caption><p>Structure of two bisbenzofuran dications with promising anti-trypanosomal activity</p></caption><graphic xlink:href="Scipharm-2011-79-389f5"></graphic></fig><fig id="f6-scipharm.2011.79.389" position="float"><label>Fig. 6.</label><caption><p>Structure of two phenylbenzofuran dications with promising anti-trypanosomal activity</p></caption><graphic xlink:href="Scipharm-2011-79-389f6"></graphic></fig><fig id="f7-scipharm.2011.79.389" position="float"><label>Fig. 7.</label><caption><p>(a) Structure of the basic nucleus of bisbenzofuran and the various substituition used to synthesized 43 congeners.</p><p>(b) stucture of compound with low cytotoxicity</p></caption><graphic xlink:href="Scipharm-2011-79-389f7"></graphic></fig><fig id="f8-scipharm.2011.79.389" position="float"><label>Fig. 8.</label><caption><p>The basic nucleus and the various substitutents used for synthesis of 49 2-phenylbenzofuran cations</p></caption><graphic xlink:href="Scipharm-2011-79-389f8"></graphic></fig><fig id="f9-scipharm.2011.79.389" position="float"><label>Fig. 9.</label><caption><p>Structures of compounds with promising anti-trypanosomal activity</p></caption><graphic xlink:href="Scipharm-2011-79-389f9"></graphic></fig><fig id="f10-scipharm.2011.79.389" position="float"><label>Fig. 10.</label><caption><p>Structures of pentamidine congeners bearing the benzofuran motif</p></caption><graphic xlink:href="Scipharm-2011-79-389f10"></graphic></fig><fig id="f11-scipharm.2011.79.389" position="float"><label>Fig. 11.</label><caption><p>Structure of furamidine and its analogue that have shown promising anti-trypanosomal properties</p></caption><graphic xlink:href="Scipharm-2011-79-389f11"></graphic></fig><fig id="f12-scipharm.2011.79.389" position="float"><label>Fig. 12.</label><caption><p>The basic nucleus and the various substitutents used for the synthesis of 43 dicationic 3,5-diphenylisoxazoles</p></caption><graphic xlink:href="Scipharm-2011-79-389f12"></graphic></fig><fig id="f13-scipharm.2011.79.389" position="float"><label>Fig. 13.</label><caption><p>Stuctures of selected dicationic 3,5-diphenylisoxazole derivatives</p></caption><graphic xlink:href="Scipharm-2011-79-389f13"></graphic></fig><fig id="f14-scipharm.2011.79.389" position="float"><label>Fig. 14.</label><caption><p>The basic nucleus and position of the various substitution used for synthesis of various analogues of 1,4-diphenyl-1<italic>H</italic>-1,2,3-triazoles series</p></caption><graphic xlink:href="Scipharm-2011-79-389f14"></graphic></fig><fig id="f15-scipharm.2011.79.389" position="float"><label>Fig. 15.</label><caption><p>Most active compound 46 of the series with promising anti-trypanosomal properties</p></caption><graphic xlink:href="Scipharm-2011-79-389f15"></graphic></fig><fig id="f16-scipharm.2011.79.389" position="float"><label>Fig. 16.</label><caption><p><italic>N</italic>,<italic>N</italic>′-bis(4-amidinophenyl)piperazine</p></caption><graphic xlink:href="Scipharm-2011-79-389f16"></graphic></fig><fig id="f17-scipharm.2011.79.389" position="float"><label>Fig. 17.</label><caption><p>Structures of compounds that showed excellent in vitro activity and selectivity</p></caption><graphic xlink:href="Scipharm-2011-79-389f17"></graphic></fig><fig id="f18-scipharm.2011.79.389" position="float"><label>Fig. 18.</label><caption><p>Two novel series active against the enzyme trypanothione reductase</p></caption><graphic xlink:href="Scipharm-2011-79-389f18"></graphic></fig><fig id="f19-scipharm.2011.79.389" position="float"><label>Fig. 19.</label><caption><p>Most active compounds of the two series</p></caption><graphic xlink:href="Scipharm-2011-79-389f19"></graphic></fig><fig id="f20-scipharm.2011.79.389" position="float"><label>Fig. 20.</label><caption><p>Lead anti-trypanosomal compound 1,2-dihydro-2,2,4-trimethiquinolin-6-yl 3,5-di-methoxybenzoate</p></caption><graphic xlink:href="Scipharm-2011-79-389f20"></graphic></fig><fig id="f21-scipharm.2011.79.389" position="float"><label>Fig. 21.</label><caption><p>Compound 9a and its prodrug 10a having promising anti-trypanosomal properties</p></caption><graphic xlink:href="Scipharm-2011-79-389f21"></graphic></fig><fig id="f22-scipharm.2011.79.389" position="float"><label>Fig. 22.</label><caption><p>The indenoisoquinoline scaffold. Structure-activity analysis was performed with substitutions at the numbered positions</p></caption><graphic xlink:href="Scipharm-2011-79-389f22"></graphic></fig><fig id="f23-scipharm.2011.79.389" position="float"><label>Fig. 23.</label><caption><p>Lead compound 12 with promising in vitro and in vivo activity</p></caption><graphic xlink:href="Scipharm-2011-79-389f23"></graphic></fig><fig id="f24-scipharm.2011.79.389" position="float"><label>Fig. 24.</label><caption><p>Basic chemical structure of fluoroquinolones</p></caption><graphic xlink:href="Scipharm-2011-79-389f24"></graphic></fig><fig id="f25-scipharm.2011.79.389" position="float"><label>Fig. 25.</label><caption><p>Most promising compounds of quinolone derivatives</p></caption><graphic xlink:href="Scipharm-2011-79-389f25"></graphic></fig><fig id="f26-scipharm.2011.79.389" position="float"><label>Fig. 26.</label><caption><p>Lead structure A</p></caption><graphic xlink:href="Scipharm-2011-79-389f26"></graphic></fig><fig id="f27-scipharm.2011.79.389" position="float"><label>Fig. 27.</label><caption><p>Tetra triazine substituted polyamine compounds</p></caption><graphic xlink:href="Scipharm-2011-79-389f27"></graphic></fig><fig id="f28-scipharm.2011.79.389" position="float"><label>Fig. 28.</label><caption><p>(a) structure of 5′-deoxy-5′-(<italic>E</italic>)-(iodomethylene)adenosine (b) structure of 6-<italic>N</italic>-cyclopropyl-5′-deoxy-5′-(<italic>E</italic>)-(iodomethylene)adenosine</p></caption><graphic xlink:href="Scipharm-2011-79-389f28"></graphic></fig><fig id="f29-scipharm.2011.79.389" position="float"><label>Fig. 29.</label><caption><p>The most active compound of morpholine series</p></caption><graphic xlink:href="Scipharm-2011-79-389f29"></graphic></fig><fig id="f30-scipharm.2011.79.389" position="float"><label>Fig. 30.</label><caption><p>N,S-blocked glutathione diesters</p></caption><graphic xlink:href="Scipharm-2011-79-389f30"></graphic></fig><fig id="f31-scipharm.2011.79.389" position="float"><label>Fig. 31.</label><caption><p>Compound 8c</p></caption><graphic xlink:href="Scipharm-2011-79-389f31"></graphic></fig><fig id="f32-scipharm.2011.79.389" position="float"><label>Fig. 32.</label><caption><p>Terphenyl diamidines and analogues</p></caption><graphic xlink:href="Scipharm-2011-79-389f32"></graphic></fig><fig id="f33-scipharm.2011.79.389" position="float"><label>Fig. 33.</label><caption><p>Fused ring dicationic compounds and their prodrugs</p></caption><graphic xlink:href="Scipharm-2011-79-389f33"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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