Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes

Abstract

Visfatin (Nicotinamide phosphoribosyltransferase) is an adipokine implicated in mediating insulin resistance and exhibiting insulin mimetic effect and therefore represents a druggable target for diabetes therapy. About 3,844 peroxisome proliferator activated receptor gamma (PPARγ) agonists documented in Chembl database were docked with PPARγ and those with binding energy of >−9 kcal/mol having experimental EC50 of 0.1 to 1 nM were selected. The candidate compounds (27) were thereafter docked with visfatin (PDB ID: 4WQ6) using AutodockVina out of which eight compounds that ranked highest in binding energy (when compared with the co-crystallized ligand of visfatin: 3TQ) were selected. Compound 25 exhibited favorable ligand-protein molecular interaction and respected Lipinski’s rule of five and interestingly from the absorption, distribution, metabolism and excretion (ADME)-Toxicity analysis the compound have enhanced pharmacological properties than the current ligand of visfatin.