2-Arylquinazolin-4(3H)-ones: A new class of α-glucosidase inhibitors. Issue 23 (1st December 2015)

• Record Type: Journal Article
• Authors: Javaid, Kulsoom; Saad, Syed Muhammad; Rasheed, Saima; Moin, Syed Tarique; Syed, Naima; Fatima, Itrat; Salar, Uzma; Khan, Khalid Mohammed; Perveen, Shahnaz; Choudhary, M. Iqbal
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 23(2015)
• Page Start: 7417
• Page End: 7421
• Publication Date: 2015-12-01
• Subjects: 2-Arylquinazolin-4(3H)-ones -- α-Glucosidase inhibition -- Structure–activity relationship -- Acarbose -- Antihyperglycemia; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.10.038
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Twenty-five derivatives of 2-arylquinazolin-4(3 H )-ones (1 –25 ) were evaluated for their yeast (Saccharomyces cerevisiae) α-glucosidase inhibitory activities. All synthetic compounds, except1 and6, were found to be several hundred fold more active (IC50 values in the range of 0.3 ± 0.01–117.9 ± 1.76 μM), than the standard drug, acarbose (IC50 = 840 ± 1.73 μM). The enzyme kinetic studies on the most active compounds12, 4, 19, and13 were performed for the determination of their modes of inhibition and dissociation constants K i . Study of the modes of inhibition of compounds12, and4 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.