In Silico Rho Kinase Inhibition and FP-Agonist Potential Study of Rotenoids Present in Boerhavia diffusa Root for Curing Uveitic Glaucoma

Abstract

The acute pathogenesis with rapid inflammation enhances the intertrabecular spaces which refers to an increase in intraocular pressure (IOP) in uveitic glaucoma. Boerhaavia diffusa (B. diffusa) plant root contains boeravinone A–J, a class of rotenoids exhibiting hepatoprotective, immunomodulatory, and anti-inflammatory actions. This article reports a comparative in silico Rho-kinase inhibition and FP-agonists study of these rotenoids. ADMET study reflects the suitability of rotenoids in terms of drug-likeness, human intestinal absorption, mitochondrial subcellular localization, and class-III toxicological compounds for real application as drug molecules. Docking study for Rho-kinase inhibition potential with 3tku-protein shows binding energies between −6.101 and −4.129 kcal/mol with an inhibition constant of 0.05–2.54 mM for boeravinone A–J against standard fasudil (−4.285 kcal/mol) molecule which has inhibition constant of 0.015 mM. Docking study for FP-agonist potential with 2f38-protein shows binding energies between −9.647 and −5.602 kcal/mol for boeravinone A–J with inhibition constants of 0.01–0.09 mM, against standard bimatoprost (−9.603 kcal/mol) and latanoprost (−10.096 kcal/mol) molecule. This MD simulation results an equilibrized dynamic behavior and stability of 3tku-boeravinone-E and 2f38-boeravinone-E complexes, under reference standards conditions. This study suggests that these rotenoids can be useful as a curative agent in uveitic glaucoma as an anti-inflammatory agent and IOP reducer.