2-Arylquinazolin-4(3H)-ones: A new class of α-glucosidase inhibitors

Kulsoom Javaid; Syed Muhammad Saad; Saima Rasheed; Syed Tarique Moin; Naima Syed; Itrat Fatima; Uzma Salar; Khalid Mohammed Khan; Shahnaz Perveen; M Iqbal Choudhary

doi:10.1016/j.bmc.2015.10.038

2-Arylquinazolin-4(3H)-ones: A new class of α-glucosidase inhibitors

Bioorg Med Chem. 2015 Dec 1;23(23):7417-21. doi: 10.1016/j.bmc.2015.10.038. Epub 2015 Oct 29.

Affiliations

¹ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
² H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: hassaan2@super.net.pk.
³ PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
⁴ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21412, Saudi Arabia.

PMID: 26552899
DOI: 10.1016/j.bmc.2015.10.038

Abstract

Twenty-five derivatives of 2-arylquinazolin-4(3H)-ones (1-25) were evaluated for their yeast (Saccharomyces cerevisiae) α-glucosidase inhibitory activities. All synthetic compounds, except 1 and 6, were found to be several hundred fold more active (IC50 values in the range of 0.3±0.01-117.9±1.76μM), than the standard drug, acarbose (IC50=840±1.73μM). The enzyme kinetic studies on the most active compounds 12, 4, 19, and 13 were performed for the determination of their modes of inhibition and dissociation constants Ki. Study of the modes of inhibition of compounds 12, and 4 were also performed using molecular modeling techniques. In brief, current study identifies a novel class of α-glucosidase inhibitors which can be further studied for the treatment of hyperglycemia and obesity.

Keywords: 2-Arylquinazolin-4(3H)-ones; Acarbose; Antihyperglycemia; Structure–activity relationship; α-Glucosidase inhibition.

Publication types

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

MeSH terms

Acarbose / pharmacology
Allosteric Site
Catalytic Domain
Enzyme Assays
Glycoside Hydrolase Inhibitors / chemical synthesis
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / pharmacology*
Kinetics
Molecular Docking Simulation
Quinazolinones / chemical synthesis
Quinazolinones / chemistry
Quinazolinones / pharmacology*
Saccharomyces cerevisiae / enzymology
Structure-Activity Relationship
alpha-Glucosidases / chemistry

Substances

Glycoside Hydrolase Inhibitors
Quinazolinones
alpha-Glucosidases
Acarbose