In silico evaluation of the estrogenic activity of flavonoids from Butea monosperma: Exploring phytoestrogenic alternatives to endogenous estrogens

Search for plant-based remedies for hypoestrogenism has validated the role of phytoestrogens as effective alternatives to endogenous estrogens. Extracts of Butea monosperma and its isolated metabolites have shown gynaecological effects pertaining to contraception, antifertility, anti-estrogenic and estrogenic potential as assessed by in vivo and in vitro assays. However, the molecular mechanism of interactions of these metabolites with estrogen receptors remains unexplored. To bridge this knowledge gap, the current research sought to characterize the pharmacological profile of flavonoids of this plant by an integrated computational approach. Twenty-nine compounds elaborated by the medicinal plant Butea monosperma were analysed for energy optimization using Guassian 16 software and taken up for molecular docking analysis by Schrodinger Maestro software and the binding affinity between the ligand and estrogenic receptors ER α - 1A52 and ER β - 3OLS were analysed. Molecular dynamic trajectories and prime mmGBSA binding free energy calculations were evaluated for ligands selected from the binding interaction score. Qikprop software and the protox server predicted ADME characteristics and toxicity of the molecules respectively. The molecular docking analysis demonstrated that six compounds displayed docking affinities comparable to that of the endogenous ligand 17β-estradiol at ER α, whereas fifteen compounds exhibited similar binding affinities at ER β. Furthermore, five compounds exhibited stronger binding affinities than 17β-estradiol toward ER α, while another five demonstrated enhanced binding affinities toward ER β, suggesting their potential as more efficacious receptor ligands. The compound catechin and isocoreopsin exhibited glide energy of -40.035 kcal/mol and -49.11 kal/mol at ER α respectively whereas 17β estradiol exhibited -52.012 kcal/mol. At ERβ, catechin and butin exhibited appreciable glide energy. These compounds were found to interact with amino acid residues HIS524, GLU353, PHE404, PHE356 and ARG346 similar to that of 17β estradiol. The study also revealed that chalcones and flavonols of Butea monosperma exhibit higher binding affinity to estrogenic receptors than the soy isoflavones genistein and daidzein.