The synthesis, structural characterization and biological evaluation of novel N-{para-(ferrocenyl) ethynyl benzoyl} amino acid and dipeptide methyl and ethyl esters as anticancer agents

A series of N-{para-(ferrocenyl) ethynyl benzoyl} amino acid and dipeptide methyl and ethyl esters 4–18 were prepared by coupling para-(ferrocenyl) ethynyl benzoic acid 3 to the amino acids GABA(OMe), GABA(OEt) and the dipeptide esters GlyGly(OMe), GlyGly(OEt), Gly-L-Ala(OMe), Gly-L-Ala(OEt), Gly-D-Ala(OMe), Gly-D-Ala(OEt), Gly-L-Leu(OEt), Gly-L-Phe(OEt), SarGly(OMe), SarGly(OEt), Sar-L-Ala(OEt), L-ProGly(OEt) and L-Pro-L-Ala(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 I.R., UV-Vis, ¹H NMR, ¹³C NMR, DEPT-135, ¹H-¹³C COSY (HMQC) spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Selected compounds 5, 7, 9, 11, 16, 17 and 18 showed micromolar activity in the H1299 NSCLC cell line, with IC₅₀ values in the range of 3.8–8.3 μM.