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.

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