Molecular docking studies of natural and synthetic compounds against human secretory PLA2 in therapeutic intervention of inflammatory diseases and analysis of their pharmacokinetic properties

Abstract

Literature survey reveals that there are several natural and synthetic anti-inflammatory compounds reported till date. As a therapeutic drug target, PLA2 inhibition is preferred over other anti-inflammatory drug targets. The pro-inflammatory effects of group X sPLA2 are acquired from multiple pathways. This study aims to identify the best anti-inflammatory compound among 22 compounds reported in literature using in silico approach. The compound ligands are subjected to docking against the target protein human sPLA2 [PDB ID: 5G3M] at the active site using AutoDock 4.2.6. Based on the Δ binding free energy and hydrogen bonding interactions, it was observed that ten compounds fit at the active site. Out of these, compound 1 (14-deoxyandrographolide) was selected as the best compound. Absorption, distribution, metabolism, and excretion (ADME) properties of the ligands are analyzed using pkCSM software available online. Compound 1 exhibited the best conformational fit when compared to the co-crystal inhibitor 4-Benzylbenzamide.