Repurposing bioenergetic modulators against protozoan parasites responsible for tropical diseases.
Identifieur interne : 000056 ( Main/Exploration ); précédent : 000055; suivant : 000057Repurposing bioenergetic modulators against protozoan parasites responsible for tropical diseases.
Auteurs : Alba Martínez-Fl Rez [Espagne] ; Melina Galizzi [États-Unis] ; Luis Izquierdo [Espagne] ; Juan M. Bustamante [États-Unis] ; Ana Rodriguez [États-Unis] ; Fernando Rodriguez [Espagne] ; Alhelí Rodríguez-Cortés [Espagne] ; Jordi Alberola [Espagne]Source :
- International journal for parasitology. Drugs and drug resistance [ 2211-3207 ] ; 2020.
Abstract
Malaria, leishmaniasis and trypanosomiasis are arthropod-borne, parasitic diseases that constitute a major global health problem. They are generally found in developing countries, where lack of access to preventive tools and treatment hinders their management. Because these parasites share an increased demand on glucose consumption with most cancer cells, six compounds used in anti-tumoral research were selected to be tested as antiparasitic agents in in vitro models of Leishmania infantum, Trypanosoma brucei, T. cruzi, and Plasmodium falciparum: dichloroacetic acid (DCA), 3-bromopyruvic acid (3BP), 2-deoxy-D-glucose (2DG), lonidamine (LND), metformin (MET), and sirolimus (SIR). No parasite-killing activity was found in L. infantum promastigotes, whereas DCA and 3BP reduced the burden of intra-macrophagic amastigotes. For T. brucei all selected compounds, but 2DG, decreased parasite survival. DCA, 2DG, LND and MET showed parasite-killing activity in T. cruzi. Finally, anti-plasmodial activity was found for DCA, 2DG, LND, MET and SIR. These results reinforce the hypothesis that drugs with proven efficacy in the treatment of cancer by interfering with ATP production, proliferation, and survival cell strategies might be useful in treating threatening parasitic diseases and provide new opportunities for their repurposing.
DOI: 10.1016/j.ijpddr.2020.07.002
PubMed: 32829099
PubMed Central: PMC7452664
Affiliations:
- Espagne, États-Unis
- Catalogne, Géorgie (États-Unis), État de New York
- Barcelone
- Université autonome de Barcelone, Université de Barcelone
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Bustamante</name><affiliation wicri:level="2"><nlm:affiliation>Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Rodriguez, Ana" sort="Rodriguez, Ana" uniqKey="Rodriguez A" first="Ana" last="Rodriguez">Ana Rodriguez</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, New York University School of Medicine, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, New York University School of Medicine, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Rodriguez, Fernando" sort="Rodriguez, Fernando" uniqKey="Rodriguez F" first="Fernando" last="Rodriguez">Fernando Rodriguez</name><affiliation wicri:level="3"><nlm:affiliation>Centre de Recerca en Sanitat Animal (CReSA)-Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Bellaterra, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre de Recerca en Sanitat Animal (CReSA)-Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Bellaterra, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="Rodriguez Cortes, Alheli" sort="Rodriguez Cortes, Alheli" uniqKey="Rodriguez Cortes A" first="Alhelí" last="Rodríguez-Cortés">Alhelí Rodríguez-Cortés</name><affiliation wicri:level="4"><nlm:affiliation>Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Electronic address: Alheli.Rodriguez@uab.cat.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author><author><name sortKey="Alberola, Jordi" sort="Alberola, Jordi" uniqKey="Alberola J" first="Jordi" last="Alberola">Jordi Alberola</name><affiliation wicri:level="4"><nlm:affiliation>Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Electronic address: Jordi.Alberola@uab.cat.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName><orgName type="university">Université autonome de Barcelone</orgName></affiliation></author></analytic><series><title level="j">International journal for parasitology. Drugs and drug resistance</title><idno type="eISSN">2211-3207</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Malaria, leishmaniasis and trypanosomiasis are arthropod-borne, parasitic diseases that constitute a major global health problem. They are generally found in developing countries, where lack of access to preventive tools and treatment hinders their management. Because these parasites share an increased demand on glucose consumption with most cancer cells, six compounds used in anti-tumoral research were selected to be tested as antiparasitic agents in in vitro models of Leishmania infantum, Trypanosoma brucei, T. cruzi, and Plasmodium falciparum: dichloroacetic acid (DCA), 3-bromopyruvic acid (3BP), 2-deoxy-D-glucose (2DG), lonidamine (LND), metformin (MET), and sirolimus (SIR). No parasite-killing activity was found in L. infantum promastigotes, whereas DCA and 3BP reduced the burden of intra-macrophagic amastigotes. For T. brucei all selected compounds, but 2DG, decreased parasite survival. DCA, 2DG, LND and MET showed parasite-killing activity in T. cruzi. Finally, anti-plasmodial activity was found for DCA, 2DG, LND, MET and SIR. These results reinforce the hypothesis that drugs with proven efficacy in the treatment of cancer by interfering with ATP production, proliferation, and survival cell strategies might be useful in treating threatening parasitic diseases and provide new opportunities for their repurposing.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32829099</PMID><DateRevised><Year>2020</Year><Month>11</Month><Day>18</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2211-3207</ISSN><JournalIssue CitedMedium="Internet"><Volume>14</Volume><PubDate><Year>2020</Year><Month>Jul</Month><Day>22</Day></PubDate></JournalIssue><Title>International journal for parasitology. Drugs and drug resistance</Title><ISOAbbreviation>Int J Parasitol Drugs Drug Resist</ISOAbbreviation></Journal><ArticleTitle>Repurposing bioenergetic modulators against protozoan parasites responsible for tropical diseases.</ArticleTitle><Pagination><MedlinePgn>17-27</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S2211-3207(20)30019-1</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ijpddr.2020.07.002</ELocationID><Abstract><AbstractText>Malaria, leishmaniasis and trypanosomiasis are arthropod-borne, parasitic diseases that constitute a major global health problem. They are generally found in developing countries, where lack of access to preventive tools and treatment hinders their management. Because these parasites share an increased demand on glucose consumption with most cancer cells, six compounds used in anti-tumoral research were selected to be tested as antiparasitic agents in in vitro models of Leishmania infantum, Trypanosoma brucei, T. cruzi, and Plasmodium falciparum: dichloroacetic acid (DCA), 3-bromopyruvic acid (3BP), 2-deoxy-D-glucose (2DG), lonidamine (LND), metformin (MET), and sirolimus (SIR). No parasite-killing activity was found in L. infantum promastigotes, whereas DCA and 3BP reduced the burden of intra-macrophagic amastigotes. For T. brucei all selected compounds, but 2DG, decreased parasite survival. DCA, 2DG, LND and MET showed parasite-killing activity in T. cruzi. Finally, anti-plasmodial activity was found for DCA, 2DG, LND, MET and SIR. These results reinforce the hypothesis that drugs with proven efficacy in the treatment of cancer by interfering with ATP production, proliferation, and survival cell strategies might be useful in treating threatening parasitic diseases and provide new opportunities for their repurposing.</AbstractText><CopyrightInformation>Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Martínez-Flórez</LastName><ForeName>Alba</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Galizzi</LastName><ForeName>Melina</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Izquierdo</LastName><ForeName>Luis</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bustamante</LastName><ForeName>Juan M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rodriguez</LastName><ForeName>Ana</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Microbiology, New York University School of Medicine, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rodriguez</LastName><ForeName>Fernando</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Centre de Recerca en Sanitat Animal (CReSA)-Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Bellaterra, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rodríguez-Cortés</LastName><ForeName>Alhelí</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Electronic address: Alheli.Rodriguez@uab.cat.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alberola</LastName><ForeName>Jordi</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Electronic address: Jordi.Alberola@uab.cat.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>07</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Int J Parasitol Drugs Drug Resist</MedlineTA><NlmUniqueID>101576715</NlmUniqueID><ISSNLinking>2211-3207</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">2-deoxy-D-glucose</Keyword><Keyword MajorTopicYN="N">3-bromopyruvate</Keyword><Keyword MajorTopicYN="N">Bionergetic modulators</Keyword><Keyword MajorTopicYN="N">Dichloroacetate</Keyword><Keyword MajorTopicYN="N">Lonidamine</Keyword><Keyword MajorTopicYN="N">Metformin</Keyword><Keyword MajorTopicYN="N">Protozoan parasites</Keyword><Keyword MajorTopicYN="N">Repurposing</Keyword><Keyword MajorTopicYN="N">Sirolimus</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>02</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>07</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>07</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>8</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>8</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>8</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32829099</ArticleId><ArticleId IdType="pii">S2211-3207(20)30019-1</ArticleId><ArticleId IdType="doi">10.1016/j.ijpddr.2020.07.002</ArticleId><ArticleId IdType="pmc">PMC7452664</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Espagne</li><li>États-Unis</li></country><region><li>Catalogne</li><li>Géorgie (États-Unis)</li><li>État de New York</li></region><settlement><li>Barcelone</li></settlement><orgName><li>Université autonome de Barcelone</li><li>Université de Barcelone</li></orgName></list><tree><country name="Espagne"><region name="Catalogne"><name sortKey="Martinez Fl Rez, Alba" sort="Martinez Fl Rez, Alba" uniqKey="Martinez Fl Rez A" first="Alba" last="Martínez-Fl Rez">Alba Martínez-Fl Rez</name></region><name sortKey="Alberola, Jordi" sort="Alberola, Jordi" uniqKey="Alberola J" first="Jordi" last="Alberola">Jordi Alberola</name><name sortKey="Izquierdo, Luis" sort="Izquierdo, Luis" uniqKey="Izquierdo L" first="Luis" last="Izquierdo">Luis Izquierdo</name><name sortKey="Rodriguez Cortes, Alheli" sort="Rodriguez Cortes, Alheli" uniqKey="Rodriguez Cortes A" first="Alhelí" last="Rodríguez-Cortés">Alhelí Rodríguez-Cortés</name><name sortKey="Rodriguez, Fernando" sort="Rodriguez, Fernando" uniqKey="Rodriguez F" first="Fernando" last="Rodriguez">Fernando Rodriguez</name></country><country name="États-Unis"><region name="Géorgie (États-Unis)"><name sortKey="Galizzi, Melina" sort="Galizzi, Melina" uniqKey="Galizzi M" first="Melina" last="Galizzi">Melina Galizzi</name></region><name sortKey="Bustamante, Juan M" sort="Bustamante, Juan M" uniqKey="Bustamante J" first="Juan M" last="Bustamante">Juan M. 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