Structure-activity relationship study of antitrypanosomal analogues of gibbilimbol B using multivariate analysis and computation-aided drug design.

dc.contributor.authorLeão, Luiz Paulo Melchior de Oliveira
dc.contributor.authorVieira, Nátalie de Barros
dc.contributor.authorOliveira, Paula P. S.
dc.contributor.authorPaula, Daniela Aparecida Chagas de
dc.contributor.authorSoares, Marisi Gomes
dc.contributor.authorSouza, Thiago Belarmino de
dc.contributor.authorZanin, João Luiz Baldim
dc.contributor.authorSilva, Thais Alves da Costa
dc.contributor.authorCardoso, André Gustavo Tempone
dc.contributor.authorDias, Danielle Ferreira
dc.contributor.authorLago, João Henrique Ghilardi
dc.date.accessioned2023-10-18T18:01:20Z
dc.date.available2023-10-18T18:01:20Z
dc.date.issued2023pt_BR
dc.description.abstractGibbilimbol B and analogues were isolated from the Brazilian plant Piper malacophyllum and displayed activity against trypomastigote forms of Trypanosoma cruzi as well as reduced toxicity against NCTC cells. These results stimulated the preparation of a series of 24 chemically related analogues to study the potential of these com- pounds against T. cruzi trypomastigotes and explore structure–activity relationships. Initially, 12 compounds were planned, maintaining the same extension of the linear side chain of gibbilimbol B and unsaturation on the C-4 position but changing the functional groups – ester and amide – and variating the substituent at the p-po- sition in the aromatic ring. Other 12 compounds were prepared using a branched side chain containing an ethyl group at the C-2 position. Overall, these structurally-related analogues demonstrated promising activity against trypomastigote forms (EC50 < 20 μM) and no mammalian cytotoxicity to fibroblasts (CC50 > 200 μM). Using multivariate statistics and machine learning analysis, aspects associated with structure/activity were related to their three-dimensional structure and, mainly, to the substituents on the aromatic ring. Obtained results sug- gested that the presence of t-butyl or nitro groups at p-position with appropriate side chains causes an alteration in the electron topological state, Van der Waals volumes, surface areas, and polarizabilities of tested compounds which seem to be essential for biological activity against T. cruzi parasites.pt_BR
dc.identifier.citationLEÃO, L. P. M. de O. et al. Structure-activity relationship study of antitrypanosomal analogues of gibbilimbol B using multivariate analysis and computation-aided drug design. Bioorganic & Medicinal Chemistry Letters, v. 83, artigo 129190, mar. 2023. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0960894X23000689>. Acesso em: 01 ago. 2023.pt_BR
dc.identifier.doihttps://doi.org/10.1016/j.bmcl.2023.129190pt_BR
dc.identifier.issn0960-894X
dc.identifier.urihttp://www.repositorio.ufop.br/jspui/handle/123456789/17600
dc.identifier.uri2https://www.sciencedirect.com/science/article/pii/S0960894X23000689pt_BR
dc.language.isoen_USpt_BR
dc.rightsrestritopt_BR
dc.subjectSynthetic analoguespt_BR
dc.subjectTrypanosoma cruzipt_BR
dc.subjectTrypomastigotespt_BR
dc.titleStructure-activity relationship study of antitrypanosomal analogues of gibbilimbol B using multivariate analysis and computation-aided drug design.pt_BR
dc.typeArtigo publicado em periodicopt_BR

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