IN SILICO AND IN VITRO ACTIVITY OF FRIEDELIN N-DERIVATIVES AGAINST PROMASTIGOTE FORMS OF Leishmania amazonensis

IN SILICO AND IN VITRO ACTIVITY OF FRIEDELIN N-DERIVATIVES AGAINST PROMASTIGOTE FORMS OF Leishmania amazonensis

Leishmaniasis is one of the six most important protozoal diseases worldwide. The potential antiprotozoal effect of pentacyclic triterpenes (TTPs), including friedelin (1), has been reported. Our goal is to create in silico models that can predict the effectiveness of TTPs against Leishmania species....

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Main Authors: Mauro Lúcio Gonçalves de Oliveira, Lucienir Pains Duarte, Grácia Divina de Fátima, Silvia Ribeiro de Souza, Misléia Rodrigues de Aguiar Gomes, Sidney Augusto Vieira-Filho, Vera Lucia de Almeida, Júlio César Dias Lopes
Format: Article
Language:English
Published: Sociedade Brasileira de Química 2025-08-01
Series:Química Nova
Subjects:
Leishmania amazonensis
friedelin N-derivatives
in silico predictions
ligand-based drug design
machine learning modeling
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-40422025000600324&lng=en&tlng=en
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Summary:Leishmaniasis is one of the six most important protozoal diseases worldwide. The potential antiprotozoal effect of pentacyclic triterpenes (TTPs), including friedelin (1), has been reported. Our goal is to create in silico models that can predict the effectiveness of TTPs against Leishmania species. We developed the Active-IT software to build these models using support-vector machine (SVM) and Naïve Bayes machine learning tools, high-quality datasets, and 3D compound structures. We synthesize N-derivatives (2-4) from friedelin to validate our theoretical results and evaluate their activity against the promastigote form of Leishmania amazonensis using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Two compounds showed appreciable inhibitory effects on L. amazonensis. We found that friedelan-3-(2,4-dinitrophenylhydrazone) (2) had the most significant inhibitory activity and the lowest half-maximal inhibitory concentration (IC50) value, supporting our developed theoretical models. Our findings showed that theoretical models created from the 3D structures of active and inactive ligands (ligand-based drug design) can provide invaluable insights into complex biological processes.
ISSN:1678-7064

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