The synthesis, structural characterization and in vitro anti-cancer activity of novel N-{6-(ferrocenyl) ethynyl-2-naphthoyl} amino acid and dipeptide ethyl esters

N-{6-(Ferrocenyl) ethynyl-2-naphthoyl} amino acid and dipeptide ethyl esters 2–8 were prepared by coupling 6-(ferrocenyl) ethynyl-2-naphthoic acid 1 to the amino acid ethyl ester GABA(OEt) and the dipeptide ethyl esters GlyGly(OEt), GlyAla(OEt), SarGly(OEt), SarAla(OEt), ProGly(OEt) and ProAla(OEt) using the standard N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole (HOBt) protocol. All the compounds were fully characterized using a combination of 1H NMR, 13C NMR, DEPT-135 and 1H–13C COSY (HMQC) spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and cyclic voltammetry (CV). Compounds, 2–8 showed micromolar activity in the H1299 NSCLC cell line, with IC50 values in the range of 3.2–7.2 μM.

Graphical abstractN-{6-(Ferrocenyl) ethynyl-2-naphthoyl} amino acid and dipeptide ethyl esters 2–8 were prepared by conventional peptide chemistry using the EDC/HOBT protocol. Compounds 2–8 exhibited cytotoxic effects on the human lung carcinoma cell line H1299, the most active derivative being N-{6-(ferrocenyl) ethynyl-2-naphthoyl}-sarcosine-l-alanine ethyl ester 6 (IC50 = 3.2 μM).Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► N-{6-(Ferrocenyl) ethynyl-2-naphthoyl}derivatives were prepared. ► The derivatives exhibited cytotoxicity on the human lung carcinoma cell line H1299. ► The most active compound had an IC50 value of 3.2 μM. ► However the ethynyl group had a negative effect on the cytotoxicity.