Natural product-inspired synthesis of coumarin-chalcone hybrids as potential anti-breast cancer agents.

Twelve novel neo-tanshinlactone-chalcone hybrid molecules were constructed through a versatile methodology involving the Horner-Wadsworth-Emmons (HWE) olefination of 4-formyl--benzo []chromen-2-ones and phosphonic acid diethyl esters, as the key step, and evaluated for anticancer activity against a series of four breast cancers and their related cell lines, MCF-7 (ER + ve), MDA-MB-231 (ER-ve), HeLa (cervical cancer), and Ishikawa (endometrial cancer). The title compounds showed excellent to moderate anti-cancer activity in a range of 6.8-19.2 µM (IC). Compounds IC = 6.8 µM and MCF-7; IC = 8.5 µM and MDA-MB-231) and IC = 14.4 µM and MCF-7; IC = 15.7 µM and MDA-MB-231) exhibited the best activity with compound showing more potent activity than the standard drug tamoxifen. Compound demonstrated a strong binding affinity with tumor necrosis factor α (TNF-α) in molecular docking studies. This is significant because TNFα is linked to MCF-7 cancer cell lines, and it enhances luminal breast cancer cell proliferation by upregulating aromatase. Additionally, virtual ADMET studies confirmed that hybrid compounds and met Lipinski's rule; displayed high bioavailability, excellent oral absorption, favorable albumin interactions, and strong penetration capabilities; and improved blood-brain barrier crossing. Based on the aforementioned results, compound has been identified as a potential anti-breast cancer lead molecule.