Organoruthenium(II) nucleoside conjugates as colon cytotoxic agents

Eleven ruthenium-nucleoside conjugates with the general formula [(η5-C5H5)Ru(PP)L][PF6] (PP = 1,2-bis(diphenylphosphino)ethane (Dppe), 2PPh3, and L = 3-N-(p-cyanobenzyl)thymidine derivative ligand) are reported. Both [(η5-C5H5)Ru(Dppe)NC-R]+ and [(η5-C5H5)Ru(PPh3)2NC-R]+ scaffolds exhibit remarkable stability towards hydrolysis. Compounds show high cytotoxicity in HCT116 colon cancer cells, with IC50 values down to 1.0 μM. Uptake competition experiments with 2′-deoxyadenosine revealed its cellular absorption to be independent of nucleoside transporters.