Green synthesis of ferrocenyl chalcones against triple negative breast cancer

Without using any solvents, a green and highly efficient protocol for the preparation of ferrocenyl chalcones has been achieved by grinding between acetylferrocene and aldehyde. In addition, their in vitro antiproliferative activity against two breast cancer cell lines MCF-7 (estrogen receptor-positive) and MDA-MB-231 (triple negative breast cancer, TNBC) was also evaluated. Most of them exhibited excellent antiproliferative activity against MDA-MB-231 cells. The structure-activity relationship (SAR) study indicated that the aldehydes unit of ferrocenyl chalcones with halogens or dimethyl substitutions were favorable for anti-TNBC activity. Among them, compound 1d (IC50 = 2.4 ± 0.1 µM) exhibited the best anti-tumor effect on MDA-MB-231 cells. An enzymatic assay indicated that compound 1d (IC50 = 2.4 µM) was a potent COX-2 inhibitor. Molecular docking suggested 1d adopted an optimal binding pose in the COX-2 active-site pocket, and the carbonyl group of 1d formed the key hydrogen bond with the Y355 residue of COX-2