An insight into anti-arthritic property OF C25H34O7 for Rheumatoid arthritis using molecular modelling and molecular dynamics approach

Abstract

Rheumatoid Arthritis (RA) is a multifactorial auto-immune disease of unknown etiology. Activation of innate immune systems including B and T lymphocytes is the earliest step in RA pathogenesis. Bruton's Tyrosine Kinase (BTK) plays a crucial role in the activation of B cells and it is being reported as one of the key drug targets for RA. Available therapeutic kinase inhibitors are associated with various side-effects, and none of them satisfies the ultimate goal of treatment options. Concurrently, several herbal compounds have been identified as potential kinase inhibitors in treating RA. In the present study, the BTK inhibition effect of bioactive compounds present in Ocimum sanctum Linn leaf extracts was determined using an in silico approach. Gas Chromatography-Mass Spectrometry was performed for methanol leaf extracts, and the bioactive compounds were screened based on anti-inflammation and anti-arthritic activity. The selected ligands were computationally synthesized and the inhibitory effect of these ligands against BTK mutant was studied through the molecular docking approach. The ligand C25H34O7 was identified as a promising herbal compound which showed a strong binding affinity towards BTK mutant with relatively three hydrogen bonds and the least docking score compared to the other selected ligands. Furthermore, molecular dynamics simulation studies were also performed using Desmond v4.0 for 25ns which revealed that the residues Ser371, Lys391, Asp500, Arg486 and Ile369 of the BTK mutant protein have the stable binding interaction between C25H34O7 throughout the simulation run. Thus, the study showed that C25H34O7 significantly formed five stable interactions which can be further investigated using in vitro and in vivo studies to verify its therapeutic potential in treating RA. Keywords: Rheumatoid arthritis, Ocimum sanctum, Bruton's tyrosine kinase, Molecular dynamics simulation, Molecular modelling