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

Publication date: June 2018Source: Beni-Suef University Journal of Basic and Applied Sciences, Volume 7, Issue 2Author(s): Olusola Olalekan Elekofehinti, Oluwamodupe Cecilia Ejelonu, Jean Paul Kamdem, Oluwaseun Benedicta Akinlosotu, Ayodeji Famuti, Damilare Desmond Adebowale, Opeyemi Iwaloye, Yetunde Irinyemi Bulu, Ige Joseph Kade, Joao Batista Teixeira RochaAbstractVisfatin (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.
Source: Beni Suef University Journal of Basic and Applied Sciences - Category: Science Source Type: research