title: 2-Arylquinazolin-4(3H)-ones: A new class of α-glucosidase inhibitors.
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.
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Kulsoom
authors.initials: K
authors.lastname: Javaid
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Syed Muhammad
authors.initials: SM
authors.lastname: Saad
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Saima
authors.initials: S
authors.lastname: Rasheed
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Syed Tarique
authors.initials: ST
authors.lastname: Moin
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Naima
authors.initials: N
authors.lastname: Syed
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Itrat
authors.initials: I
authors.lastname: Fatima
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Uzma
authors.initials: U
authors.lastname: Salar
authors.affiliation: 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.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.affiliation: PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Perveen
authors.affiliation: 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.
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D020909:Acarbose / Q000494:pharmacology; D000495:Allosteric Site; D020134:Catalytic Domain; D057075:Enzyme Assays; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D062105:Molecular Docking Simulation; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000737:chemistry
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D052999:Quinazolinones; D000520:alpha-Glucosidases; D020909:Acarbose
keywords: 2-Arylquinazolin-4(3H)-ones; Acarbose; Antihyperglycemia; Structure–activity relationship; α-Glucosidase inhibition