Abstract
PURPOSE: The enzyme Cyclooxygenases (COX-1 and COX-2) catalyze the formation of prostaglandin, a mediator of the inflammatory pathway. Inflammation related pathological conditions may be alleviated by targeting the Cox enzymes.COX-2 inhibitors that are currently available in the market causes undesirable side effects. Our present study focuses on the in-silico inhibition of COX -2 enzyme by the phytocompounds from Albizia amara and Phyla nodiflora. METHODS: The phytochemicals present in Albizia amara and Phyla nodiflora were analyzed for their COX-2 inhibition potential. Eight compounds from Albizia amara and eleven compounds from Phyla nodiflora obtained from GC-MS analysis was used for the current study. Molecular docking was performed using AutoDock vina. The crystal structure of COX-2 (PDB ID: 5IKR) was obtained from Protein data bank. PyMol was used to remove any solvent, organic and inorganic molecules. Energy minimization of the protein was carried out using SPDBV software. Geometrical optimizations of the ligands were performed using Avogadro software. Celecoxib was used as the positive control. ADMET properties of the compounds were analyzed using SwissADME and ProtoxII online servers. Molecular mechanics/generalized born surface area (MM/GBSA) calculations were performed to evaluate the binding efficiency. Molecular dynamics of the protein and protein-ligand complex was studied for about 100 ns using Desmond package of Schrodinger suite. RESULTS: Among the eighteen compounds, Squalene present in both the plants showed a better binding energy of -7.7 kcal/mol, when compare to other phytocompounds present in the extract. The control celecoxib showed a binding energy of about - 9.4 kcal/mol. The toxicity and ADMET properties of squalene indicated that it is non-toxic and followed Lipinski's rule. Molecular Dynamics (MD) analysis showed that the binding of squalene to the enzyme was stable. CONCLUSION: Squalene could potentially inhibit COX2 and o wing to its properties, squalene can be formulated in gels/creams and could be possibly used for external edema and inflammation.