In Silico approach for exploring the potential of few drugs against Leishmaniasis

Leishmaniasis, classified as a neglected tropical disease (NTD), is spread through the bite of female sand flies, presenting itself in the forms of cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) as the primary clinical manifestations. MAPK or mitogen-activated protein kinase is an important signaling pathway in the protozoan parasites that involves cellular activities such as stress regulation, apoptosis, and cell differentiation which is important for parasite survival. In this research, a new therapeutic strategy was developed through an in-silico-drug repurposing approach on synthetic compounds to discover potential as an inhibitor of 4QNY. Approximately 100 synthetic compounds were selected based on prior research. Their structures were obtained from the Zinc 15 database. These compounds were then evaluated using Lipinski’s rule of five and ADMET properties to filter out any undesirable molecules. Protein structures were retrieved from the RCSB protein data bank, and the MapK (Mitogen-Activated Protein Kinase) from Leishmania donovani (PDB ID: 4QNY) was used as protein/macromolecule for docking of ligand. After that, the chosen ligands underwent blind docking to predict their inhibition towards 4QNY. From molecular docking simulation, Irinotecan shows favorable characteristics as a drug candidate with a significant binding energy score of -10.41 Kcal/mol and estimated inhibition constant (Ki) of 23.29 nM.