Molecular Docking Studies and In-silico ADMET Profile Analysis of Triphala Plant constituents Morin and 9, 10-anthraquinone as Potential Inhibitors of human Estrogen Receptor Alpha

Abstract

The expanding global burden of cancer demands novel treatment options. Herbal medicine offers a viable alternative to conventional cancer treatment. Breast cancer is frequently diagnosed cancer among women all over the world. Normal breast cells and specific breast cancer cells containestrogen and progesterone receptors. Estrogen and progesterone bind to receptors and stimulate cancer cell proliferation and expansion with growth factors (e.g., oncogenes and mutated gene suppressors). Tamoxifen, raloxifene, andtoremifene are among the most frequently used drugs for breast cancer, whereas estrogen continues to be produced in breast cancer cells. These medications primarily function against theestrogen binding to theestrogenreceptors on these cells. Protein-ligand interaction plays a major role in structural drug design. In this study, the molecular interactions between theHuman estrogen receptor alpha (PDB ID: 2IOK), and the two ligands isolated from Triphala Ayurvedic formulation morin, and 9,10-anthraquinone, an endogenous estrogen receptor ligand, estradiol, and the three economically available breast cancer drug, tamoxifen, raloxifene, and toremifene using the AutodockVina software tool. The ADMET properties of these substances were determinedusing popular web-based software tools that include preADMET, admetSAR, Molinspiration, and SwissADME.The present available anti-cancer drugs have so many side effects. The present work is aimed at determining the efficacy ofestrogen receptor inhibitors and the safety profile of morin, anthraquinone molecules isolated from Triphalapolyherbal formulation by in-silico methods. The binding energies (Kcal/mol) of ligands with human estrogen receptor were calculated as follows: morin (-9.0), 9,10-anthraquinone (-8.7), estradiol (-10.1), tamoxifen (-9.6), raloxifene (-9.8) and toremifene (-8.9). The resultssupported the drug-like properties of the molecules tested and they are likely to have a therapeutic effect.Further,in vivo and pre-clinical trials of the most active compound are also worthwhile for producing effective inhibitors.