Additional functionality for plecstatin-1-analogous anticancer Ru(η-p-cymene)Cl complexes.

The bioactivity of organometallic compounds can be enhanced by modifying the ligand to achieve higher potency or an altered mode of action. Here, we conjugated amino acids to pyridine-2-carbothioamides (PCAs) and formed their Ru(cym)Cl (cym = η-p-cymene) organometallics, as confirmed by mass spectrometry, NMR spectroscopy and elemental analysis. The in vitro antiproliferative activities of ligands 1-4 and complexes 1a-4a were established against human non-small cell lung carcinoma (NCI-H460), cervical carcinoma (SiHA), colorectal carcinoma (HCT116) and colon adenocarcinoma (SW480) cell lines. Complexes 1a-3a showed no activity but 4a was moderately potent with an IC value of 35 μM in NCI-H460 cells. Organoruthenium compound 4a was also more active than its PCA ligand 4 and the clinically investigated Ru complex KP1339 in NCI-H460 cells.