文章基本信息

标题：Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes
本地全文：下载
作者：Olusola Olalekan Elekofehinti ; Olusola Olalekan Elekofehinti ; Oluwamodupe Cecilia Ejelonu 等
期刊名称：Beni-Suef University Journal of Basic and Applied Sciences
印刷版ISSN：2314-8535
电子版ISSN：2314-8543
出版年度：2018
卷号：7
期号：2
页码：241-249
DOI：10.1016/j.bjbas.2018.02.007
语种：English
出版社：Elsevier
摘要：Highlights•Obesity and fat accumulation predominantly in White adipose tissue are important risk factors for type 2 diabetes mellitus.•Adipose tissue is regarded as the site for lipid storage and also a mobilizing tissue with an important role in the control of energy homeostasis.•Visfatin is a newly discovered hormone mainly synthesized and secreted in visceral fat (WAT).•Visfatin is implicated in mediating insulin resistance and exhibiting insulin mimetic effect.•Visfatin may represent a druggable target for diabetes therapy.•Agonists of visfatin are presented with better binding interactions and ADMET properties than current ligand of visfatin.AbstractVisfatin (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 EC50of 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.
关键词：Nicotinamide phosphoribosyltransferase;Visfatin molecular docking;Type 2 diabetes;Adipokines