Molecular docking studies of phytochemicals from piper species as potential dual inhibitor of group X secreted phospholipase A2 (SPLA2-X) and Cyclooxygenase-2 (COX-2)

Abstract

The group X secreted phospholipase A2 (sPLA2-X) and cyclooxygenase-2 (COX-2) are enzymes involved in biosynthesis of prostaglandins, a potent mediator of inflammation. The sPLA2-X hydrolysed membrane phospholipids to arachidonic acid and further converted into prostaglandins by COX-2. Previous studies showed that naturally occurring phytochemicals reduced prostaglandins level in cell culture and animal models. In the present study, we investigated molecular interaction between ten phytochemicals from Piper species, with sPLA2-X and COX-2 using in silico molecular docking approaches for potential anti-inflammatory properties. The selected phytochemicals were subjected to docking simulation using Autodock 4.2 software. Docking results were compared with reference drugs including indomethacin, celecoxib and varespladib. The result identified cubebin as potential dual inhibitor of sPLA2-X and COX-2. This compound makes contact with protein target by forming hydrogen bonds and hydrophobic interactions. Cubebin is also predicted to have a lower COX-2 binding energy than indomethacin and celecoxib. Interaction of cubebin with sPLA2-X and COX-2 amino acids indicates the potential as dual enzyme inhibition activities. 1,*,