Identification of novel quinazolin-4(3H)-ones as inhibitors of thermolysin, the prototype of the M4 family of proteinases.
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.
Khan
Mahmud Tareq Hassan
MT
Medical Pharmacology and Toxicology, Department of Medical Biology, Faculty of Health Science, University of Tromsø, N-9037 Tromsø, Norway.
Khan
Rasool
R
Wuxiuer
Yimingjiang
Y
Arfan
Mohammad
M
Ahmed
Manzoor
M
Sylte
Ingebrigt
I
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
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