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Synthesis and Evaluation of a Ruthenium-based Mitochondrial Calcium Uptake Inhibitor
Published on: October 26, 2017
Cyclometalated ruthenium (II) complexes induced HeLa cell apoptosis through intracellular reductive injury
Xufeng Zhu1, Qiang Sun2, Xinhua Guo2
1Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Zhanjiang, Guangdong 524023, China; The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong 524023, China.
Abstract:
The main challenge of cancer chemotherapy is the resistance of tumor cells to oxidative damage. Herein, we proposed a novel antitumor strategy: cyclic metal‑ruthenium (Ru) complexes mediate reductive damage to kill tumor cells. We designed and synthesized Ru(II) complexes with β-carboline as ligands: [Ru (phen)2(NO2-Ph-βC)](PF6) (RuβC-7) and [Ru(phen)2(1-Ph-βC)](PF6) (RuβC-8). In vitro experimental results showed that RuβC-7 and RuβC-8 can inhibit cell proliferation, promote mitochondrial abnormalities, and induce DNA damage. Interestingly, RuβC-7 with SOD activity could reduce intracellular reactive oxygen species (ROS) levels, while RuβC-8 has the opposite effect. Accordingly, this study identified the reductive damage mechanism of tumor apoptosis, and may provide a new ideas for the design of novel metal complexes.

