Synthesis, characterisation and biological evaluation of N-(ferrocenyl)naphthoyl amino acid esters as anticancer agents

Abstract

A series of N-(ferrocenyl)naphthoyl amino acid esters 5-18 has been prepared by coupling ferrocenyl naphthoic acids 3-4 to alpha-amino acids and linear amino acids in the presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBt). The compounds were fully characterised by a range of NMR spectroscopic techniques, UV-Vis spectroscopy, mass spectrometry and cyclic voltammetry. X-ray crystallographic studies of the intermediate compounds 1-2 were also performed. Biological evaluation of the intermediates 1-2 and N-(ferrocenyl)naphthoyl amino acid esters 5-18 was performed in the H1299 non-small cell lung cancer (NSCLC) cell line and the Sk-Mel-28 metastatic melanoma cell line. The intermediates 1-2 failed to produce an effect in either cell line. Compounds 5-18 exhibited a strong anti-proliferative effect in the H1299 cell line, whilst the Sk-Mel-28 cells were slightly more resistant to these compounds. N-(6-ferrocenyl-2-naphthoyl)-gamma-aminobutyric acid ethyl ester 17 shows a particularly high activity in both the H1299 cell line (IC(50) = 0.62 +/- 0.07 microM) and the Sk-Mel-28 cell line (IC(50) = 1.41 +/- 0.04 microM).