Structure based virtual screening of MDPI database: discovery of structurally diverse and novel DPP-IV inhibitors

Omprakash Tanwar; Lalima Tanwar; Md Shaquiquzzaman; Md Mumtaz Alam; Mymoona Akhter

doi:10.1016/j.bmcl.2014.05.076

Structure based virtual screening of MDPI database: discovery of structurally diverse and novel DPP-IV inhibitors

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3447-51. doi: 10.1016/j.bmcl.2014.05.076. Epub 2014 Jun 2.

Authors

Omprakash Tanwar¹, Lalima Tanwar², Md Shaquiquzzaman¹, Md Mumtaz Alam¹, Mymoona Akhter³

Affiliations

¹ Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Bioinformatics Infrastructure Facility (BIF), Jamia Hamdard, New Delhi 110062, India.
² School of Biochemistry, DAVV, Khandwa Road, Indore, India.
³ Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Bioinformatics Infrastructure Facility (BIF), Jamia Hamdard, New Delhi 110062, India. Electronic address: mymoonaakhter@gmail.com.

PMID: 24948564
DOI: 10.1016/j.bmcl.2014.05.076

Abstract

Inhibition of dipeptidyl peptidase IV (DPP-IV) has been emerged as a promising approach for the treatment of type 2 diabetes (T2D). Structure based virtual screening (SBVS) of Molecular Diversity Preservation International (MDPI) database was performed using Glide and Gold against DPP-IV enzyme. Six promising hits were identified and tested for DPP-IV inhibition. Three compounds were found to be active at low micromolar concentration. The 3-(1-hydrazinyl-1-(phenylamino)ethyl)-4-hydroxy-1-methylquinolin-2(1H)-one (compound A) was found to be the most potent hit with an IC50 of 0.73 μM. These three compounds (A, B and D) were then assessed for their glucose lowering effects in glucose fed hyperglycemic female Wistar rats. The glucose lowering effects of compounds also confirms their potential as anti-diabetic agents. The present study demonstrates a successful utilization of in silico SBVS tools in identification of novel and potential DPP-IV inhibitor.

Keywords: DPP-IV inhibitors; Glucagon-like peptide-1; Molecular Diversity Preservation International; Type-2 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus, Experimental / drug therapy*
Diabetes Mellitus, Experimental / enzymology
Diabetes Mellitus, Experimental / metabolism
Dipeptidyl Peptidase 4 / metabolism*
Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis
Dipeptidyl-Peptidase IV Inhibitors / chemistry
Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Drug Discovery*
Female
High-Throughput Screening Assays*
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / pharmacology*
Molecular Structure
Rats
Rats, Wistar
Structure-Activity Relationship

Substances

Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Dipeptidyl Peptidase 4