Identification of natural cytochalasins as leads for neglected tropical diseases drug discovery

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dc.contributor.authorValli, Marilia
dc.contributor.authorSouza, Julia Medeiros
dc.contributor.authorChelucci, Rafael Consolin
dc.contributor.authorBiasetto, Carolina Rabal [UNESP]
dc.contributor.authorAraujo, Angela Regina [UNESP]
dc.contributor.authorda Silva Bolzani, Vanderlan [UNESP]
dc.contributor.authorAndricopulo, Adriano Defini
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2023-07-29T13:24:09Z
dc.date.available2023-07-29T13:24:09Z
dc.date.issued2022-10-01
dc.description.abstractInvestigating the chemical diversity of natural products from tropical environments is an inspiring approach to developing new drug candidates for neglected tropical diseases (NTDs). In the present study, phenotypic screenings for antiprotozoal activity and a combination of computational and biological approaches enabled the identification and characterization of four cytochalasins, which are fungal metabolites from Brazilian biodiversity sources. Cytochalasins A-D exhibited IC50 values ranging from 2 to 20 μM against intracellular Trypanosoma cruzi and Leishmania infantum amastigotes, values comparable to those of the standard drugs benznidazole and miltefosine for Chagas disease and leishmaniasis, respectively. Furthermore, cytochalasins A-D reduced L. infantum infections by more than 80% in THP-1 cells, most likely due to the inhibition of phagocytosis by interactions with actin. Molecular modelling studies have provided useful insights into the mechanism of action of this class of compounds. Furthermore, cytochalasins A-D showed moderate cytotoxicity against normal cell lines (HFF-1, THP-1, and HepG2) and a good overall profile for oral bioavailability assessed in vitro. The results of this study support the use of natural products from Brazilian biodiversity sources to find potential drug candidates for two of the most important NTDs.en
dc.description.affiliationLaboratory of Medicinal and Computational Chemistry (LQMC) Centre for Research and Innovation in Biodiversity and Drug Discovery (CIBFar) São Carlos Institute of Physics (IFSC) University of São Paulo (USP), SP
dc.description.affiliationNuclei of Bioassays Biosynthesis and Ecophysiology of Natural Products (NuBBE) Department of Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), SP
dc.description.affiliationUnespNuclei of Bioassays Biosynthesis and Ecophysiology of Natural Products (NuBBE) Department of Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), SP
dc.description.sponsorshipUniversidade Estadual Paulista
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2013/ 07600-3
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0275002
dc.identifier.citationPLoS ONE, v. 17, n. 10 October, 2022.
dc.identifier.doi10.1371/journal.pone.0275002
dc.identifier.issn1932-6203
dc.identifier.scopus2-s2.0-85139570536
dc.identifier.urihttp://hdl.handle.net/11449/247727
dc.language.isoeng
dc.relation.ispartofPLoS ONE
dc.sourceScopus
dc.titleIdentification of natural cytochalasins as leads for neglected tropical diseases drug discoveryen
dc.typeArtigo

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