Antileishmanial activity in silico and in vitro of semi-synthetic derivatives obtained from natural products

Abstract

American cutaneous leishmaniasis (ACL) continues to be a public health problem in at least 85 countries around the world. Since medications for the treatment of ACL have toxic side effects, there is a need to search for new active molecules from plants. The objective of this study was to investigate the in vitro and in silico antileishmanial activity of semi-synthetic derivatives obtained from natural products. The bioassay used the species of Leishmania (L.) amazonensis and Leishmania (V.) guyanensis cultivated in supplemented RPMI medium. The 50% inhibitory concentration (IC₅₀) was obtained by inhibiting promastigotes exposed to the solutions naringenin, aminoguanidine, CNFD, FGS-3, FGS-16 and FGS-18 at concentrations of 50 to 3.125 µg.mL^-1. In the experiment, 0.2% DMSO and pentamidine isethionate at 3 µg.mL^-1 were used as the controls for 24, 48 and 72 h, in triplicate. Regarding the interaction of the active ingredients with the enzymatic targets (2WP5 and 2VPM), molecular docking was used with the aid of the AutoDock Vina v.1.2.5. As for the derivatives FGS-16 and FGS-18, these presented spectra within those described in the literature. Regarding the 50% cytotoxic concentration (CC₅₀) in cells after 72 h, FGS-18=329.9±0.3 µg.mL^-1. The IC₅₀ of FGS-16=0.7±0.2 µg.mL^-1 for L. guyanensis and 0.5±0.6 µg.mL^-1 for L. amazonensis.Therefore, the selectivity index was 45.7 (L. guyanensis) and 64 (L. amazonensis). Furthermore, the molecule presented three hydrogen bonds for the 2WPM target. Therefore, the FGS-16 proved to be the most promising derivative with antileishmanial activity.