Covalent interaction of Ru(terpy)(tmephen)Cl+ with DNA: A potential ruthenium-based anticancer drug

The use of ruthenium complexes in antitumor therapy was launched two decade s ago. In view of their low toxicity and good selectivity for solid tumor m etastasis, ruthenium complexes have great potential as alternative drugs to cisplatin in cancer chemotherapy. A series of monochloro ruthenium complex es, Ru(terpy) (NN)Cl+ (NN, bidentate nitrogen ligand), containing different electron-donating groups were prepared. The reactivity towards the formati on of Ru-DNA adduct were revealed by gel mobility shift assay. Their DNA bi nding sites of Ru(terpy)(tmephen)Cl+ were located predominantly at the puri ne residues i.e., guanine and adenine, by terminating DNA elongation in vit ro using PCR and primer extension techniques. Surprisingly, the ability of Ru(terpy)(tmephen)Cl+ to inhibit cell growth was found to be approximately two times better than that of a known cross-linking agent, Ru(bpy)(2)Cl-2. Therefore, the increase in liability of the chloro ligand was demonstrated to improve the reactivity of these ruthenium complexes towards the covalent bond formation in Ru-DNA adducts and result also in a significant inhibiti on of cell growth. Based on our results, these ruthenium complexes modified with electron-rich groups provide new consideration in the tune of rutheni um-based drugs in cancer chemotherapy.