In silico study of selected lignins as COX-2 inhibitors

Abstract

Natural products present in medicinal plants play an important role in several biological processes, many of which alleviate and control inflammation-related diseases. These have been linked to an action involving direct inhibitory binding, especially on COX-2 protein. The present study reports the in-silico study of selected lignins for COX-2 inhibition and its correlation with its anti-inflammatory activities. We aim to understand lignin's structural and conformational features for inhibitory capability and illustrate their binding mode in the COX-2 active site. For this purpose, six lignins, namely pinoresinol, syringaresinol, 1-acetoxypinoresinol, berchemol, 8-Hydroxypinoresinol, and (-)-Olivil have been analyzed through ADME (absorption, distribution, metabolism, excretion) prediction, molecular docking study, molecular dynamic simulation, and binding free energy analysis. ADME study supports the potential biological activity of all selected lignins. At the same time, the described docking scores, the interaction profile, and the obtained conformations suggested berchemol as the best inhibitor for COX-2 protein, followed by 8-Hydroxypinoresinol and pinoresinol. 50 ns of the molecular dynamic simulation was then used to evaluate the stability of docked protein-ligand complexes and to estimate the conformational changes occurring during protein-ligand interaction. From the RMSD, RMSF, the number of hydrogen bonds, SASA, and MM/PBSA binding free energy score analysis, we have found that syringaresinol showed a good binding free energy score of-154.06±15.08 kJ/mol and displayed excellent pharmacological and structural properties to be drug candidate for the anti-inflammatory disease. In addition, MD results indicated shows that syringaresinol established more favorable interactions than rofecoxib. It is fixed in the COX-2 active site by the key residue Tyr-355 and stabilized by Ser-530.