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 IC50 values ranging from 0.0115 μM (compound 3) to 122,637 μM (compound 29). Compound 3 [3-phenyl-2-(trifluoromethyl) quinazolin-4(3H)-one] (IC50 = 0.0115 μM) and compound 35 [3-(isopropylideneamino)-2,2-dimethyl-2,3-dihydroquinazolin-4 (1H)-one] (IC50 = 0.2477 μM) were found to be the most potent inhibitors.

Interaction of compound 3 [3-phenyl-2-(trifluoromethyl) quinazolin-4(3H)-one] with thermolysin.Figure optionsDownload as PowerPoint slide