Synthesis, characterisation and biological evaluation of N-(ferrocenyl)naphthoyl amino acid esters as anticancer agentsCCDC reference numbers 718596 and 775339. For crystallographic data in CIF or other electronic format see DOI: 10.1039/c0dt00377h

• Main Authors: Mooney, Áine, Corry, Alan J, Ruairc, Cliodhna Ní, Mahgoub, Thamir, O'Sullivan, Dermot, O'Donovan, Norma, Crown, John, Varughese, Sunil, Draper, Sylvia M, Rai, Dilip K, Kenny, Peter T. M
• Format: Article
• Language: English
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c0dt00377h

A series of N -(ferrocenyl)naphthoyl amino acid esters 5-18 has been prepared by coupling ferrocenyl naphthoic acids 3-4 to α-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)-γ-aminobutyric acid ethyl ester 17 shows a particularly high activity in both the H1299 cell line (IC 50 = 0.62 ± 0.07 μM) and the Sk-Mel-28 cell line (IC 50 = 1.41 ± 0.04 μM). N -(6-ferrocenyl-2-naphthoyl)-γ-aminobutyric acid ethyl ester has a potent anti-proliferative effect in both the H1299 NSCLC and Sk-Mel-28 melanoma cell lines.