Identification of potential anti-leishmanial compounds from natural sources against citrate synthase enzyme using structure-based drug designing

Abstract

Leishmaniasis, an infectious parasitic disease, has been targeted for elimination by World Health Organization. This study, natural compounds were selected from the ZINC 15 database for virtual screening against Leishmania donovani citrate synthase (LdCS). Four molecules, i.e., Staurosporine, Solasodine, Cromolyn, and Oxetacaine selected based on binding free energy (> -9.0 kcal/mol) and interaction with the active site residues of LdCS. Molecular dynamics simulation and MM/PBSA analysis were also carried out to reinforce their binding activities. The simulation trajectory analysis showed that all molecules bind to the active site of LdCS with strong and stable affinities. Docking and simulation studies also revealed that binding pockets contain hydrophobic contacts and optimum hydrogen bonds. Two molecules, Cromolyn and Oxetacaine, were pharmacologically profiled as drug-like based on ADMET properties. These natural compounds may act as inhibitors of LdCS and potential anti-leishmanials. © 2023 Elsevier B.V.