Hibiscus sabdariffa anthocyanins are potential modulators of estrogen receptor alpha activity with favourable toxicology: a computational analysis using molecular docking, ADME/Tox prediction, 2D/3D QSAR and molecular dynamics simulation

The estrogen hormone receptor (ER) mediated gene expression mainly regulate the development and physiology of the primary and secondary reproductive system alongside bone-forming, metabolism and behaviour. Over-expressed ER is associated with several pathological conditions and play a crucial role in breast cancer occurrence, progression and metastasis. Hibiscus sabdariffa L. or roselle is a rich source of naturally occurring polyphenolic compounds that reportedly have robust estrogenic activity. However, the estrogen-like ingredient of the plant remains ambiguous. This study has screened a library of already recorded and less-explored compounds of Hibiscus sabdariffa for their estrogen receptor binding affinity and safety using a suite of computational methods that include protein-ligand docking, ADME and Toxicity prediction, and 2D/3D QSAR. The study revealed that the estrogen-receptor binding potential of Pelargonidin, Delphinidin, Cyanidin, and Hibiscetin are more efficient than popular breast cancer drugs, Tamoxifen and Raloxifene. Besides, the compounds exhibited favourable toxicological parameters with potent bioactivity towards binding ER-α subunit. Thus, these compounds can serve as prototypes for designing novel Selective Estrogen Receptor Modulator molecules with a few structural modifications. This is the first report exploring the phytochemical basis of estrogenic activity of Hibiscus sabdariffa L.Communicated by Ramaswamy H. Sarma.