Computational study to discover potent phytochemical inhibitors against drug target, squalene synthase from Leishmania donovani
Padmika Madushanka Wadanambi, Uthpali Mannapperuma
Abstract
AIMS: squalene synthase (LdSQS) enzyme, a drug target. MAIN METHODS: spp. Their evolutionary relationships were studied by generating phylogenetic tree. Homology modeling method was used to build a three dimensional model of the protein. The validated model was explored by docking simulation with the phytochemicals of interest to identify the most potent inhibitors. Two reported inhibitors were used as references in the virtual screening. The top hit compounds (binding energy less than -9 kcal/mol) were further subjected to intermolecular interaction analysis, pharmacophore modeling, pharmacokinetic and toxicity prediction. KEY FINDINGS: prediction criteria for oral bioavailability. SIGNIFICANCE: Based on the current study, these hits can be further structurally optimized and validated under laboratory conditions to develop antileishmanial drugs.