title: Inhibition of mammalian aspartate transcarbamylase by quinazolinone derivatives.
abstract: Quinazolinone derivatives have been studied as both in vitro and in vivo inhibitors of aspartate transcarbamylase (ATCase). In vitro treatment of mammalian ATCase with four compounds revealed that they inhibited enzyme activity and that 2-phenyl-1,3-4(H)benzothiazin-4-thione was the most potent one. This compound acts as a noncompetitive inhibitor towards both aspartate and carbamoyl phosphate. The values of the inhibition constant (K(i)) indicate that this compound exerts a potent inhibitory effect upon ATCase activity. Moreover, in vivo treatment with different doses of these derivatives showed also an inhibitory effect upon ATCase, the relative activity being decreased by 40%-58% with a 1 mg dose. These data support the inhibition of ATCase by quinazolinone derivatives as a new type of inhibitor for the enzyme.
authors.affiliation: Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt. m_balbaa@hotmail.com
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Balbaa
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Megeed
authors.forename: Thoria
authors.initials: T
authors.lastname: Diab
authors.forename: Hamdy
authors.initials: H
authors.lastname: Mansour
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001221:Aspartate Carbamoyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D007700:Kinetics; D052999:Quinazolinones / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D052999:Quinazolinones; D001221:Aspartate Carbamoyltransferase