A structure-based drug design approach for the identification of novel selective Cyclooxygenase-2 inhibitors using resveratrol analogues as lead molecules

Abstract

Therapeutic areas for selective cyclooxygenase-2 inhibitors include inflammatory conditions and cancer. A study has demonstrated that hydroxylated analogues of resveratrol, which is found in red wine, inhibit cyclooxygenase-2 selectively. This study aimed to design in silico novel selective cyclooxygenase-2 inhibitors using two of these resveratrol analogues, namely 3,3’,4’,5-tetrahydroxystilbene and 3,3’,4,4’,5,5’-hexahydroxystilbene, as molecular templates. Two hundred molecules were generated de novo from each of these analogues. The binding affinities (pKd) of the novel molecules ranged from 9.70 to 10.00. In total, 10% of the molecules were compliant with Lipinski Rules, and hence, were orally bioavailable. The Lipinski Rules compliant molecules with high affinities can be included in libraries of selective cyclooxygenase-2 inhibitors to be used in highthroughput screening.