Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as Leishmania mexicana Inhibitors

Cutaneous leishmaniasis (CL) is a public health problem affecting more than 98 countries worldwide. No vaccine is available to prevent the disease, and available medical treatments cause serious side effects. Additionally, treatment failure and parasite resistance have made the development of new drugs against CL necessary. In this work, a virtual screening of natural products from the BIOFACQUIM and Selleckchem databases was performed using the method of molecular docking at the triosephosphate isomerase (TIM) enzyme interface of Leishmania mexicana (L. mexicana). Finally, the in vitro leishmanicidal activity of selected compounds against two strains of L. mexicana, their cytotoxicity, and selectivity index were determined. The top ten compounds were obtained based on the docking results. Four were selected for further in silico analysis. The ADME-Tox analysis of the selected compounds predicted favorable physicochemical and toxicological properties. Among these four compounds, S-8 (IC(50) = 55 µM) demonstrated a two-fold higher activity against the promastigote of both L. mexicana strains than the reference drug glucantime (IC(50) = 133 µM). This finding encourages the screening of natural products as new anti-leishmania agents.