Arene-ruthenium(Ⅱ) Complexes With Nitrogen-containing Heterocyclic Derivatives: Synthesis, Characterization And Anticancer Activity

Water-soluble arene-Ru(II) complexes providing both hydrophilicas well as hydrophobic properties hold a high potential for thedevelopment of metal-based anticancer drugs for its high selectivity, lowcytotoxicity and antimetastatic properties. We synthesized scores ofarene-Ru(II) complexes with nitrogen-containing heterocyclic derivatives,characterized their structure, and studied the interaction of thesecompounds with DNA by UV-visible spectroscopy and electrochemicalmethodes. The results show that these compounds do interact with DNA,which is useful for understanding the cancer pathogenesis and themechanism of anti-cancer drug treatment, and give some guidance for thesynthesis and the in vitro screening of new drugs.5-Fluorouracil (5-Fu), first synthesized in1957, is one of theantitumor agents frequently used for treating solid tumors. However, the clinical applications of5-Fu are subjected to great limitations because ofits short plasma half-life，poorly tumor selectivity，intestinal toxicity andso on. To tackle these problems, numerous modifications of the5-Fustructure have been performed to develop new prodrugs of5-Fu as leadcompounds with high efficiency and low toxicity.Consideration of the research progress of arene-Ru(II) complexesand5-Fu derivatives, we used the coupling principles of drug design andthe law of coordination and substitution reaction to introduce5-Fumolecule into arene-Ru(II) complexes through ester-central and terminalligands, and built single-core arene-Ru(II) complexes with multi-activecentres. The in vitro anticancer activity of these compounds indicatedthat the introduction of5-Fu molecules into arene-Ru(II) complexes bypyridine ligand can reduce the toxicity of5-Fu molecule, which couldprovide the experimental data and application prospects for the researchand development of synergistic anti-cancer new drug.