title: Identification of novel quinazolin-4(3H)-ones as inhibitors of thermolysin, the prototype of the M4 family of proteinases.
abstract: A combinatorial series of novel quinazolin-4(3H)-ones were synthesised and their structures were established based on spectroscopic data (IR, NMR, EI-MS, and FAB-MS). The compounds were tested for inhibition of the zinc metalloproteinase thermolysin (TLN) utilizing a chemical array-based approach. Some of the compounds were found to inhibit TLN, with IC(50) values ranging from 0.0115 microM (compound 3) to 122,637 microM (compound 29). Compound 3 [3-phenyl-2-(trifluoromethyl) quinazolin-4(3H)-one] (IC(50)=0.0115 microM) and compound 35 [3-(isopropylideneamino)-2,2-dimethyl-2,3-dihydroquinazolin-4 (1H)-one] (IC(50)=0.2477 microM) were found to be the most potent inhibitors.
authors.affiliation: Medical Pharmacology and Toxicology, Department of Medical Biology, Faculty of Health Science, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Mahmud Tareq Hassan
authors.initials: MT
authors.lastname: Khan
authors.forename: Rasool
authors.initials: R
authors.lastname: Khan
authors.forename: Yimingjiang
authors.initials: Y
authors.lastname: Wuxiuer
authors.forename: Mohammad
authors.initials: M
authors.lastname: Arfan
authors.forename: Manzoor
authors.initials: M
authors.lastname: Ahmed
authors.forename: Ingebrigt
authors.initials: I
authors.lastname: Sylte
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D008968:Molecular Conformation; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013820:Thermolysin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C552764:3-(isopropylideneamino)-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-one; C552763:3-phenyl-2-(trifluoromethyl)quinazolin-4(3H)-one; D011480:Protease Inhibitors; D011799:Quinazolines; D052999:Quinazolinones; D013820:Thermolysin