title: 2-Arylquinazolin-4(3H)-ones: Inhibitory Activities Against Xanthine Oxidase.
abstract: 2-Arylquinazolin-4(3H)-ones (1-25) were synthesized, and evaluated for their xanthine oxidase inhibitory activity. Significant to moderate activities were exhibited by the compounds 1-3, 7, 9, 13-15, 19-21, and 23 with IC50 between 2.80 - 28.13 µM as compared to the standard allopurinol (IC50 (IC50 = 2.01 ± 0.01 µM). Compounds 4-6, 8, 11-12, 16-18, 22, and 24 demonstrated a weak activity with IC50 values 44.60 - 112.60 µM. Nonetheless, compounds 10 and 25 did not show any activity. Amongst all derivatives, compound 2, containing a C-4´ dimethylamino group, was the most potent inhibitor of the enzyme with an IC50 value comparable to the standard. Kinetics studies on the most active compounds (2, 7, 9, 14, 15, 19, and 20) were conducted in order to determine their modes of inhibition and dissociation constants Ki. Some of the compounds of 2-arylquinazolin-4(3H)-one series were thus identified as potential leads for further studies towards the treatment of hyperuricemia and gout.
authors.forename: Humaira
authors.initials: H
authors.lastname: Zafar
authors.forename: Syed M
authors.initials: SM
authors.lastname: Saad
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Perveen
authors.lastname: Arshia
authors.forename: Rizwana
authors.initials: R
authors.lastname: Malik
authors.forename: Ajmal
authors.initials: A
authors.lastname: Khan
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan. khalid.khan@iccs.edu.
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Khan
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan. hej@cyber.net.pk.
authors.forename: Muhammad I
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D016475:3T3 Cells; D000818:Animals; D057075:Enzyme Assays; D016166:Free Radical Scavengers / Q000737:chemistry / Q000633:toxicity; D005966:Glucuronidase / Q000037:antagonists & inhibitors; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000633:toxicity; D007502:Iron Chelating Agents / Q000737:chemistry / Q000633:toxicity; D007700:Kinetics; D051379:Mice; D052999:Quinazolinones / Q000737:chemistry* / Q000633:toxicity; D013778:Tetrazolium Salts; D013844:Thiazoles; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D065089:Glycoside Hydrolase Inhibitors; D007502:Iron Chelating Agents; D052999:Quinazolinones; D013778:Tetrazolium Salts; D013844:Thiazoles; D014969:Xanthine Oxidase; D000520:alpha-Glucosidases; D005966:Glucuronidase; C022616:thiazolyl blue