Ferrocenyl compounds derived from the reaction of phenylamines with ferrocenecarbonyl chloride: Synthesis, characterisation and their biological activity

• Eight ferrocenyl derivatives were synthesized and fully characterised.
• The anticancer activities of the eight compounds were assessed in the two breast cancer cell lines, MCF-7 and MDA-MB-231.
• It seems that compounds of less negative reduction potential showed better activity.
• The activity of compounds (4 and 8) bearing methyl substituent may be associated with their demethylation.

Eight ferrocenyl derivatives were synthesized and characterised by NMR, elemental analyses and X-ray single crystal diffraction analysis. The anticancer activities of the eight compounds were assessed where applicable in the two breast cancer cell lines, MCF-7 and MDA-MB-231. It was found that the cytotoxicity of N-Phenyl-N-(2-Methyl-4-Methoxyphenyl)ferrocenecarboxamide (4) and N,N-bis(4-Methoxyphenyl)ferrocenecarboxamide (8) correlates to their relatively positive reduction potentials, which may suggest that the cytotoxicity stems from their involvement in electron transfer process. Furthermore, comparing the activity of N,N-bis(phenyl)ferrocenecarboxamide (3) to that of compounds 4 and 8 suggest that their methoxyl group may undergo demethylation under physiological conditions to generate biologically active species and thus they exhibited better activity in the two breast cancer cell lines compared to compound 3.

Inhibit or not inhibit? The methoxy group on the phenyl skeletons of the compounds matters in their activity against the two breast cancer cell lines, MCF-7 and MDA-MB-231.Figure optionsDownload as PowerPoint slide