title: Structure based virtual screening of MDPI database: discovery of structurally diverse and novel DPP-IV inhibitors.
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.
authors.affiliation: Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Bioinformatics Infrastructure Facility (BIF), Jamia Hamdard, New Delhi 110062, India.
authors.forename: Omprakash
authors.initials: O
authors.lastname: Tanwar
authors.affiliation: School of Biochemistry, DAVV, Khandwa Road, Indore, India.
authors.forename: Lalima
authors.initials: L
authors.lastname: Tanwar
authors.affiliation: Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Bioinformatics Infrastructure Facility (BIF), Jamia Hamdard, New Delhi 110062, India.
authors.forename: Md
authors.initials: M
authors.lastname: Shaquiquzzaman
authors.affiliation: Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Bioinformatics Infrastructure Facility (BIF), Jamia Hamdard, New Delhi 110062, India.
authors.forename: Md Mumtaz
authors.initials: MM
authors.lastname: Alam
authors.affiliation: 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.
authors.forename: Mymoona
authors.initials: M
authors.lastname: Akhter
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D005260:Female; D057166:High-Throughput Screening Assays; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D018819:Dipeptidyl Peptidase 4
keywords: DPP-IV inhibitors; Glucagon-like peptide-1; Molecular Diversity Preservation International; Type-2 diabetes