Open AccessDESIGN, SYNTHESIS AND COX1/2 INHIBITORY ACTIVITY OF NEW QUINAZOLINE-5-ONE DERIVATIVES
Author(s) -
Ahmed S. Aboraia,
Mohammed A. Hara,
Mostafa H. Abdelrahman,
Mohamed M. Amin,
Osama I. El-Sabbaghab
Publication year - 2017
Publication title -
journal of advances in chemistry
Language(s) - English
Resource type - Journals
ISSN - 2321-807X
DOI - 10.24297/jac.v13i12.6019
Subject(s) - ic50 , chemistry , celecoxib , cyclooxygenase , diclofenac , enzyme , docking (animal) , quinazoline , selectivity , active site , stereochemistry , pharmacology , enzyme inhibitor , inhibitory postsynaptic potential , cox 2 inhibitor , in vitro , biochemistry , catalysis , biology , medicine , nursing
A new series of 1-(4-Acetylphenyl)-7,7-dimethyl-3-(substitutedphenyl)-1,2,3,4,7,8-octahydroquinazolin-5(6H)-ones (6-15) were synthesized and tested against COX-1 and COX-2 enzymes. Those compounds exhibited strong interaction at the COX-2 binding site and poor interaction at the COX-1 active site. Subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assay; most of the compounds especially compounds 6, 7, 12, 13, and 16 exhibited potent anti-inflammatory effects, selective COX-2 inhibition, with half-maximal inhibitor concentration (IC50) values of 0.22–1.42 μM and selectivity index (SI) values of 6.16–14.18 compared with celecoxib (IC50 = 0.05 μM and COX-2 SI: 296), diclofenac (IC50 = 0.8 μM and COX-2 SI: 4.87), and indomethacin (IC50 = 0.49 μM and COX-2 SI: 0.08) as reference drugs. Docking study has been carried out to confirm the binding affinity and selectivity of the most active compound (compound 6) to COX-2 enzyme.