Organoruthenium(ii) nucleoside conjugates as colon cytotoxic agents

Abstract

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.