Investigation of anti-breast cancer potential of a Coral-derived heterocyclic molecule Capillobenzofuranol by inhibiting Estrogen Receptor-α

Abstract

Abstract Estrogen receptor α (ER-α) plays a crucial role in the start and progression of breast cancer. ER-α stimulates the expression of oncogenic proteins including Cyclin D1 and c-Myc while inhibiting the expression of cell cycle inhibitors like P21. ER-α has critical functions in the development, survival, and architecture of cancer cells and the regulation of gene expression in these cells. Estrogen receptors are also linked to ER-mediated breast cancer and its progression. In this study, we focused on blocking the active binding site of estradiol (E1), which binds to the ER-α and is known to cause breast cancer. We conducted a virtual screening for approximately 50 natural chemicals that were shown to be overexpressed in ER-α. A target-based approach for drug design was used in this study, which included high throughput screening using molecular docking via AutoDock vina, based on the best-docked phytochemical nutraceuticals, and further investigation employed into the stability and efficacy of the ER-α during 100 ns molecular dynamics and simulation. The results of the post-simulation analysis and binding energy calculation in MMGBSA demonstrated that the nutraceuticals possessed a superior potential for ER inhibition in a concentration dependent manner. Due to its strong affinity for the Estrogen Receptor-protein, it could be an active site inhibitor for ER-mediated breast cancer.