IN SILICO AND IN VITRO ACTIVITY OF FRIEDELIN N-DERIVATIVES AGAINST PROMASTIGOTE FORMS OF Leishmania amazonensis
Year: 2025
Type: article
Abstract: 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.
Source: Química Nova
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $330
OpenAlex ID: W4412559053