High-throughput virtual screening and quantum mechanics approach to develop imipramine analogues as leads against trypanothione reductase of leishmania

Abstract

Visceral leishmaniasis (VL) has been considered as one of the most fatal form of leishmaniasis which affects 70 countries worldwide. Increased drug resistance in Indian subcontinent urged the need of new antileishmanial compounds with high efficacy and negligible toxicity. Imipramine compounds have shown impressive antileishmanial activity. To find out most potent analogue from imipramine series and explore the inhibitory activity of imipramine, we docked imipramine analogues (n=93,328) against trypanothione reductase in three sequential modes. Furthermore, 98 ligands having better docking score than reference ligand were subjected to ADME and toxicity, binding energy calculation and docking validation. Finally, Molecular dynamic and single point energy was estimated for best two ligands. This study uncovers the inhibitory activity of imipramine against Leishmania parasites.

Keywords: ADMET; Imipramine; Molecular dynamics; Trypanothione reductase; Visceral leishmaniasis.