In Vitro and In Silico Determination of Some N-ferrocenylmethylaniline Derivatives as Anti-Proliferative Agents Against MCF-7 Human Breast Cancer Cell Lines

Background: Since the binding of estradiol to its receptor promotes breast cancer cell proliferation (in the ER+ tumours), many molecules targeting this protein have been synthesized to counteract the estradiol action. Ferrocene derivatives have proved their efficiency against hormone-dependent breast cancer cells (MCF-7).

Objective: In this study, we aimed to find new ferrocene derivatives having pharmacochemistry properties as potential drugs against human breast cancer cells.

Methods: A series of 29 N-ferrocenylmethylaniline derivatives A0-A28 were synthesised, and their anti-proliferative activity against both hormone-dependent (MCF-7) and independent (MDA-MB 231) human breast cancer cell lines were performed using the MTT test. Molecular docking and drug-likeness prediction were also performed for the five most active derivatives towards MCF-7. A QSAR model was also developed for the perdition of the anti-proliferative activity against MCF-7 cell lines using molecular descriptors and MLR analysis.

Results: All studied derivatives demonstrated better cytotoxicity against MCF-7 compared to the MDA-MB-231 cell lines, and compounds A2, A9, A14, A17 and A27 were the most potent ones but still less active than the standard anticancer drug, crizotinib. The QSAR study revealed good predictive ability, as shown by R2 cv = 0.848.

Conclusion: In vitro and in silico results indicated that derivatives A2, A9, A14, A17, and A27 possess the highest anti-proliferative activity; these results can be used to design more potent N-ferrocenylmethylaniline derivatives as anti-proliferative agents.