The synthesis, structural characterization and in vitro anti-cancer activity of novel 1-alkyl-1′-N-para-(ferrocenyl) benzoyl dipeptide esters

• 1-Alkyl-1′-N-para-(ferrocenyl) benzoyl dipeptide ester derivatives were prepared.
• They exhibited cytotoxicity on the human lung carcinoma cell line H1299.
• Alkylation of the cyclopentadiene ring increases the cytotoxicity.
• The cytotoxicity decreases with an increase of the size of the alkyl group.

1-Alkyl-1′-N-para-(ferrocenyl) benzoyl dipeptide esters 4–12 were prepared by coupling the alkyl ferrocenyl benzoic acids 1–3 to the dipeptide ethyl esters Gly-L-Ala(OEt), Gly-L-Leu(OEt) and Gly-L-Phe(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). Selected compounds showed micromolar activity in the H1299 NSCLC cell line, with IC50 values in the range of 4.5–6.6 μM.

1-Alkyl-1′-N-para-(ferrocenyl) benzoyl dipeptide ethyl esters 4–12 were prepared by conventional peptide chemistry using the EDC/HOBT protocol. Compounds 4–12 exhibited cytotoxic effects on the human lung carcinoma cell line H1299, the most active derivative being 1-methyl-1′-N-{para-(ferrocenyl)-benzoyl}-glycine-l-alanine ethyl ester 4 (IC50 = 4.5 μM).Figure optionsDownload as PowerPoint slide