The synthesis, structural characterization and in vitro anticancer activity of novel 1-alkyl-1′-N-meta-(ferrocenyl) benzoyl dipeptide esters and novel 1-alkyl-1′-N-ortho-(ferrocenyl) benzoyl dipeptide esters

• 1-Alkyl-1′-N-meta and ortho-(ferrocenyl) benzoyl dipeptide esters were prepared.
• They exhibited cytotoxicity on the human lung carcinoma cell line H1299.
• Compound 7 displayed an IC50 value of 2.6 μM.
• The cytotoxicity decreases with an increase of the size of the alkyl group.

1-Alkyl-1′-N-meta-(ferrocenyl) benzoyl dipeptide esters 7–18 and 1-alkyl-1′-N-ortho-(ferrocenyl) benzoyl dipeptide esters 19–30 were prepared by coupling the alkyl ferrocenyl benzoic acids 1–6 to the dipeptide ethyl esters Gly-Gly(OEt), 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. The alkyl groups employed in the synthesis were methyl, ethyl and propyl. The compounds were characterized using a combination of 1H NMR, 13C NMR, DEPT-135 and 1H-13C COSY (HMQC) spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Selected compounds showed micromolar activity in the H1299 NSCLC cell line, with IC50 values in the range of 2.6–20.1 μM.

1-Alkyl-1′-N-meta and ortho-(ferrocenyl) benzoyl dipeptide ethyl esters 7–30 were prepared by conventional peptide chemistry using the EDC/HOBT protocol. Compounds 7–30 exhibited cytotoxic effects on the human lung carcinoma cell line H1299. 1-Methyl-1′-N-{meta-(ferrocenyl)-benzoyl}-glycine-glycine ethyl ester 7 had an IC50 value of 2.6 μM.Figure optionsDownload as PowerPoint slide