Study on antitumor activity of three ruthenium arene complexes in vitro

Three ruthenium arene complexes, namely {[(η⁶-p-cymene)Ru(Cl)]₂(dpb)}(PF₆)₂ (1), [(η⁶-p-cymene)Ru(dpb)Cl](PF₆) (2) and [(η⁶-p-cymene) Ru(dpb)py](PF₆) (3) (dpb = 2,3-bis(2-pyridyl)benzo-quinoxaline, py = pyridine), were synthesized and their antitumor properties were introduced. Complexes 1-3 were characterized by ¹H NMR, MS, and elemental analysis. As a binuclear ruthenium structure, the absorption of metal ligand electron transfer (MLCT) of 1 extended to 700 nm. Complex 1 was significantly hydrolyzed under dark conditions. The cytotoxicity in vitro study showed that complexes 1 and 2 are more toxic to human lung cancer cells (A549) and human cervial cancer cells (Hela) than cisplatin. Moreover, there was almost no cross-resistance between complex 1-2 and cisplatin. Under the irradiation at 478 nm, complexes 1-3 all produced singlet oxygen (¹O₂), and the ¹O₂ quantum yield of complex 1 in PBS is the highest among complexes 1-3. Complex 1 also produced ¹O₂ under 600 nm light irradiation. DNA gel electrophoresis showed that 1 caused the photocleavage of plasmid DNA. The hydrolysis rate of complex 1 was accelerated under light (λ > 600 nm). And the phototoxicity of complex 1 to Hela cells under light (λ > 600 nm) was much greater than its dark toxicity, which may be due to its generation of ¹O₂ and the promotion of its hydrolysis under long-wave light irradiation.