Document Type: Research article
Pharmaceutical Research Center, School of pharmacy, Mashhad University of Medical Sciences, Iran
Bioinformatics Research Center, Sabzevar University of Medical Sciences, School of Medicine, Sabzevar, Iran.
Design of selective cyclooxygenase-2 (COX-2) inhibitors is still a challenging task because of active site similarities between COX isoenzymes. To help with this issue, we tried to generate a 3D-QSAR (3 dimensional quantitative structure activity relationship) model that might reflect the essential features of COX-2 active sites. Compounds in a series of resveratrol derivatives inhibitors with reported biological activity against COX-2 were used to construct a predictive comparative molecular similarity indices (CoMSIA) model. A CoMSIA model with acceptable internal and external predictability was developed and employed to design new not yet synthesized molecules with improved activity and selectivity toward COX-2. Finally, molecular docking of the inhibitors in COX-2 active site demonstrated the possible ability of proposed compounds to inhibit COX-2, selectively.