Synthesis, characterization and evaluation of novel ferrocenylmethylamine derivatives as cytotoxic agents

The present report describes a new series of amide functionalized 20‐ and 30‐aminomethylferrocene derived from ferrocenylmethylamine. The compounds 1a‐5a and 1b‐5b were characterized by microanalysis, 1H, 13C NMR, UV–visible, fluorescence, FTIR, thermogravimetric and crystallographic techniques. The X‐ray analysis demonstrated the ability of these molecules to form various intermolecular hydrogen bonding interactions, as verified by Hirshfeld surface analysis. All the compounds were evaluated against MCF 7, IMR 32, HepG2 and immortal L132 cell lines by MTT assay and the results were compared with cisplatin. Interestingly, many compounds were very active against all the investigated cell lines and proved to be more potent as cytotoxic agents than cisplatin. The western blot, gene expression, mitochondrial membrane potential and flow cytometry study were used to investigate the mode of action of these derivatives as antitumor agents. The results showed apoptotic property of the compounds by modulating inflammatory pathway against human tumor cells of different origin. We performed the density functional theory calculations and molecular docking to rationalize the experimental results. Synthesis of new derivatives of ferrocenylmethylamine and their ability to show anticancer activity in low micromolar concentrations have been investigated. Based on various biological parameters and molecular docking study, the mode of action of these derivatives and structure‐activity relationship have been established.