
A multi-species phenotypic screening assay for leishmaniasis drug discovery shows that active compounds display a high degree of species-specificity
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor | Centro de Biotecnologia | pt_BR |
dc.contributor.author | Alcantara, Laura M. | pt_BR |
dc.contributor.author | Ferreira, Thalita Camêlo da Silva | pt_BR |
dc.contributor.author | Fontana, Vanessa | pt_BR |
dc.contributor.author | Chatelain, Eric | pt_BR |
dc.contributor.author | Moraes, Carolina Borsoi | pt_BR |
dc.contributor.author | Freitas-Junior, Lucio Holanda Gondim | pt_BR |
dc.date.accessioned | 2020-07-09T21:28:00Z | - |
dc.date.available | 2020-07-09T21:28:00Z | - |
dc.date.issued | 2020 | pt_BR |
dc.identifier.citation | Alcantara LM., Ferreira TCS, Fontana V, Chatelain E, Moraes CB, Freitas-Junior LHG. A multi-species phenotypic screening assay for leishmaniasis drug discovery shows that active compounds display a high degree of species-specificity. Molecules. 2020 May;25(11):2551. doi:10.3390/molecules25112551. | pt_BR |
dc.identifier.uri | https://repositorio.butantan.gov.br/handle/butantan/3058 | - |
dc.description.abstract | High genetic and phenotypic variability between Leishmania species and strains within species make the development of broad-spectrum antileishmanial drugs challenging. Thus, screening panels consisting of several diverse Leishmania species can be useful in enabling compound prioritization based on their spectrum of activity. In this study, a robust and reproducible high content assay was developed, and 1280 small molecules were simultaneously screened against clinically relevant cutaneous and visceral species: L. amazonensis, L. braziliensis, and L. donovani. The assay is based on THP-1 macrophages infected with stationary phase promastigotes and posterior evaluation of both compound antileishmanial activity and host cell toxicity. The profile of compound activity was species-specific, and out of 51 active compounds, only 14 presented broad-spectrum activity against the three species, with activities ranging from 52% to 100%. Notably, the compounds CB1954, Clomipramine, Maprotiline, Protriptyline, and ML-9 presented pan-leishmanial activity, with efficacy greater than 70%. The results highlight the reduced number of compound classes with pan-leishmanial activity that might be available from diversity libraries, emphasizing the need to screen active compounds against a panel of species and strains. The assay reported here can be adapted to virtually any Leishmania species without the need for genetic modification of parasites, providing the basis for the discovery of broad spectrum anti-leishmanial agents. | pt_BR |
dc.description.sponsorship | (DNDi) Drugs for Neglected Diseases Initiative | pt_BR |
dc.description.sponsorship | Swiss Agency for Development and Cooperation (SDC) | pt_BR |
dc.description.sponsorship | UK Aid | pt_BR |
dc.description.sponsorship | (MSF) Médecins sans frontières | pt_BR |
dc.description.sponsorship | (CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico | pt_BR |
dc.description.sponsorship | (FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo | pt_BR |
dc.format.extent | 2551 | pt_BR |
dc.language.iso | English | pt_BR |
dc.relation.ispartof | Molecules | pt_BR |
dc.rights | Open access | pt_BR |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | pt_BR |
dc.title | A multi-species phenotypic screening assay for leishmaniasis drug discovery shows that active compounds display a high degree of species-specificity | pt_BR |
dc.type | Article | pt_BR |
dc.rights.license | CC BY | pt_BR |
dc.identifier.doi | 10.3390/molecules25112551 | pt_BR |
dc.identifier.url | https://doi.org/10.3390/molecules25112551 | pt_BR |
dc.contributor.external | (LNBio) Laboratório Nacional de Biociências | pt_BR |
dc.contributor.external | (USP) Universidade de São Paulo | pt_BR |
dc.contributor.external | (DNDi) Drugs for Neglected Diseases Initiative | pt_BR |
dc.contributor.external | University of Liverpool | pt_BR |
dc.contributor.external | (UNIFESP) Universidade Federal de São Paulo | pt_BR |
dc.identifier.citationvolume | 25 | pt_BR |
dc.identifier.citationissue | 11 | pt_BR |
dc.subject.keyword | Leishmania | pt_BR |
dc.subject.keyword | leishmaniasis drug discovery | pt_BR |
dc.subject.keyword | phenotypic screening | pt_BR |
dc.subject.keyword | Leishmania species | pt_BR |
dc.relation.ispartofabbreviated | Molecules | pt_BR |
dc.identifier.citationabnt | v. 25, n. 11, 2551, mai. 2020 | pt_BR |
dc.identifier.citationvancouver | 2020 May;25(11):2551 | pt_BR |
dc.contributor.butantan | Ferreira, Thalita Camêlo da Silva|:Aluno|:Centro de Biotecnologia|: | pt_BR |
dc.contributor.butantan | Freitas-Junior, Lucio Holanda Gondim|:Colaborador|:|:Autor de correspondência | pt_BR |
dc.sponsorship.butantan | (CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦140907/2013-0 | pt_BR |
dc.sponsorship.butantan | (CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦140831/2015-0 | pt_BR |
dc.sponsorship.butantan | Drugs for Neglected Diseases Initiative (DNDi)¦¦ | pt_BR |
dc.sponsorship.butantan | (FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦15/10436-6 | pt_BR |
dc.sponsorship.butantan | Médecins sans frontières (MSF)¦¦ | pt_BR |
dc.sponsorship.butantan | Swiss Agency for Development and Cooperation (SDC)¦¦ | pt_BR |
dc.sponsorship.butantan | UK Aid¦¦ | pt_BR |
dc.identifier.bvscc | BR78.1 | pt_BR |
dc.identifier.bvsdb | IBProd | pt_BR |
dc.description.dbindexed | Yes | pt_BR |
item.fulltext | Com Texto completo | - |
item.grantfulltext | open | - |
item.languageiso639-1 | English | - |
item.openairetype | Article | - |
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