Andrographolide: a diterpenoid from Cymbopogon schoenanthus identified as a new hit compound against Trypanosoma cruzi using machine learning and experimental approaches

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dc.contributorLab. Fisiopatologiapt_BR
dc.contributor.authorBarbosa, Henriquept_BR
dc.contributor.authorEspinoza, Gabriel Zarzanapt_BR
dc.contributor.authorAmaral, Maiarapt_BR
dc.contributor.authorCardoso, Andre Gustavo Temponept_BR
dc.date.accessioned2024-01-11T14:47:58Z-
dc.date.available2024-01-11T14:47:58Z-
dc.date.issued2023pt_BR
dc.identifier.citationBarbosa H, Espinoza GZ, Amaral M, Cardoso AGT. Andrographolide: a diterpenoid from Cymbopogon schoenanthus identified as a new hit compound against Trypanosoma cruzi using machine learning and experimental approaches. J Chem Inf Model. 2023 Dec; 64(7):2565-2576. doi:10.1021/acs.jcim.3c01410.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/5215-
dc.description.abstractAmerican Trypanosomiasis, also known as Chagas disease, is caused by the protozoan Trypanosoma cruzi and exhibits limited options for treatment. Natural products offer various structurally complex metabolites with biological activities, including those with anti-T. cruzi potential. The discovery and development of prototypes based on natural products frequently display multiple phases that could be facilitated by machine learning techniques to provide a fast and efficient method for selecting new hit candidates. Using Random Forest and k-Nearest Neighbors, two models were constructed to predict the biological activity of natural products from plants against intracellular amastigotes of T. cruzi. The diterpenoid andrographolide was identified from a virtual screening as a promising hit compound. Hereafter, it was isolated from Cymbopogon schoenanthus and chemically characterized by spectral data analysis. Andrographolide was evaluated against trypomastigote and amastigote forms of T. cruzi, showing IC50 values of 29.4 and 2.9 μM, respectively, while the standard drug benznidazole displayed IC50 values of 17.7 and 5.0 μM, respectively. Additionally, the isolated compound exhibited a reduced cytotoxicity (CC50 = 92.8 μM) against mammalian cells and afforded a selectivity index (SI) of 32, similar to that of benznidazole (SI = 39). From the in silico analyses, we can conclude that andrographolide fulfills many requirements implemented by DNDi to be a hit compound. Therefore, this work successfully obtained machine learning models capable of predicting the activity of compounds against intracellular forms of T. cruzi.pt_BR
dc.format.extent2565-2576pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofJournal of Chemical Information and Modelingpt_BR
dc.rightsRestricted accesspt_BR
dc.titleAndrographolide: a diterpenoid from Cymbopogon schoenanthus identified as a new hit compound against Trypanosoma cruzi using machine learning and experimental approachespt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1021/acs.jcim.3c01410pt_BR
dc.identifier.urlhttps://doi.org/10.1021/acs.jcim.3c01410pt_BR
dc.contributor.external(UFABC) Universidade Federal do ABCpt_BR
dc.contributor.external(USP) Universidade de São Paulopt_BR
dc.contributor.external(UFMG) Universidade Federal de Minas Geraispt_BR
dc.identifier.citationvolume64pt_BR
dc.identifier.citationissue7pt_BR
dc.relation.ispartofabbreviatedJ Chem Inf Modelpt_BR
dc.identifier.citationabntv. 64, n. 7, p. 2565-2576, dez. 2023pt_BR
dc.identifier.citationvancouver2023 Dec; 64(7):2565-2576pt_BR
dc.contributor.butantanCardoso, Andre Gustavo Tempone|:Pesquisador|:Lab. Fisiopatologiapt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
item.openairetypeArticle-
item.languageiso639-1English-
item.grantfulltextnone-
item.fulltextSem Texto completo-
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