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

摘要

A series of N-(ferrocenylmethyl amino acid) fluorinated benzene-carboxamide derivatives 4b-i and 5b-i 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, ~(13)C NMR, ~(19)F NMR, distortionless enhancement by polarization transfer (DEPT)-135, ~1H-~1H correlation spectroscopy (COSY) and ~1H-~(13)C 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 IC_(50) value of 2.84 μm. Compounds 4i, 5h and 5i had lower IC_(50) values than that found for the clinically employed anticancer drug cisplatin (IC_(50) = 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.