The synthesis, structural characterization and biological evaluation of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives as potential anticancer agents

Abstract

A series of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i and 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i have been synthesized by coupling ferrocenylmethyl amine 3 with various substituted N‐(fluorobenzoyl) amino acid derivatives using the standard N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride, 1‐hydroxybenzotriazole protocol. The amino acids employed in this study were glycine and L‐alanine. All of the compounds were fully characterized using a combination of 1H NMR, 13C NMR, 19F NMR, distortionless enhancement by polarization transfer (DEPT)‐135, 1H–1H correlation spectroscopy (COSY) and 1H–13C COSY (heteronuclear multiple‐quantum correlation) spectroscopy. The compounds were biologically evaluated on the oestrogen‐positive MCF‐7 breast cancer cell line. Compounds 4g, 4i, 5h and 5i exhibited cytotoxic effects on the MCF‐7 breast cancer cell line. N‐(Ferrocenylmethyl‐L‐alanine)‐3,4,5‐trifluorobenzene‐carboxamide (5h) was the most active compound, with an IC50 value of 2.84 μm. Compounds 4i, 5h and 5i had lower IC50 values than that found for the clinically employed anticancer drug cisplatin (IC50 = 16.3 μm against MCF‐7). Guanine oxidation studies confirmed that 5h was capable of generating oxidative damage via a reactive oxygen species‐mediated mechanism. Copyright © 2013 John Wiley & Sons, Ltd.