Computer-aided drug design of optimal ratio selective inhibition of COX-1 and COX-2

1026-1034The selective inhibition of both COX-1 and COX-2 by NSAIDS results in beneficial as well as harmful effects. To reduce the side effects, a natural phytochemical having coumarin moiety has been selected for optimal ratio inhibition of COX-1 and COX-2. Based on docking studies and information obtained from interaction analysis, structure-based virtual screening has been performed by designing 150 analogues with structural diversity. The compound 58 has been found to be a potent selective inhibitor for both COX-1 and COX-2 with the optimal ratio. The docking studies reveal that these features show good interaction with amino acid His43, Gln42, Lys468, His119 and Thr119 and also show further π-alkyl hydrophobic interaction with Lys 468, π-sulfur interaction with His94, His96 in the binding site of COX-1 and COX-2. Toxicity and drug likeness have been estimated by using OSIRIS molecular property explorer tool. These compounds have been found to be free from toxicity risk, exhibit better positive drug likeness and drug score compared to reference compound with favorable values of ClogP, solubility, molecular weight and TPSA