Design and synthesis of quinazoline-3,4-(4H)-diamine endowed with thiazoline moiety as new class for DPP-4 and DPPH inhibitor

Zulphikar Ali; Md Jawaid Akhtar; Md Rafi Haider; Ahsan Ahmed Khan; Anees Ahmad Siddiqui; M Shahar Yar

doi:10.1016/j.bioorg.2017.02.004

Design and synthesis of quinazoline-3,4-(4H)-diamine endowed with thiazoline moiety as new class for DPP-4 and DPPH inhibitor

Bioorg Chem. 2017 Apr:71:181-191. doi: 10.1016/j.bioorg.2017.02.004. Epub 2017 Feb 10.

Authors

Zulphikar Ali¹, Md Jawaid Akhtar¹, Md Rafi Haider¹, Ahsan Ahmed Khan¹, Anees Ahmad Siddiqui¹, M Shahar Yar²

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India. Electronic address: yarmsy@rediffmail.com.

PMID: 28215601
DOI: 10.1016/j.bioorg.2017.02.004

Abstract

New N3-benzylidene (substituted)-2-phenyl-N4-(thiazol-2-yl)-quinazoline-3,4-(4H)-diamine derivatives were design and synthesized by a sequence of reactions starting from appropriate 6-methyl anthranilic acid. The title compounds were screened for in vitro dipeptidyl peptidase IV (DPP-4) inhibitory activity and diphenyl-2-picryl-hydrazyl (DPPH) assay and results showed significant to good activity in compared to Linagliptin for antidiabetic activity and Ascorbic acid for antioxidant activity. Compound 7g (IC₅₀=0.76nM) exhibited most promising DPP-4 inhibitory activity and also showed good antioxid and result. Docking study was also performed to provide an insight about the binding mode into binding sites of DPP-4 enzyme. Hopefully in future, compound 7g could be used as a lead compound for developing new antidiabetic agent with good antioxidant property.

Keywords: DPP-4 inhibitors; DPPH; Molecular docking; Quinazoline; Thiazoline.

Publication types

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

MeSH terms

Animals
Antioxidants / chemical synthesis
Antioxidants / chemistry*
Antioxidants / pharmacology
Antioxidants / therapeutic use
Biphenyl Compounds / antagonists & inhibitors
Diabetes Mellitus, Experimental / drug therapy*
Diabetes Mellitus, Experimental / enzymology
Dipeptidyl Peptidase 4 / metabolism
Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis
Dipeptidyl-Peptidase IV Inhibitors / chemistry*
Dipeptidyl-Peptidase IV Inhibitors / pharmacology
Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
Drug Design*
Free Radicals / antagonists & inhibitors
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / chemistry*
Hypoglycemic Agents / pharmacology
Hypoglycemic Agents / therapeutic use
Molecular Docking Simulation
Picrates / antagonists & inhibitors
Quinazolines / chemical synthesis
Quinazolines / chemistry*
Quinazolines / pharmacology
Quinazolines / therapeutic use
Rats, Wistar
Thiazoles / chemical synthesis
Thiazoles / chemistry
Thiazoles / pharmacology
Thiazoles / therapeutic use

Substances

Antioxidants
Biphenyl Compounds
Dipeptidyl-Peptidase IV Inhibitors
Free Radicals
Hypoglycemic Agents
Picrates
Quinazolines
Thiazoles
1,1-diphenyl-2-picrylhydrazyl
Dipeptidyl Peptidase 4