Novel NHC-coordinated ruthenium(II) arene complexes achieve synergistic efficacy as safe and effective anticancer therapeutics.

European Journal of Medicinal Chemistry
Chao ChenHangxiang Wang

Abstract

There is an urgent need for more effective, less toxic cancer therapy agents. Motivated by this need, we synthesized a small panel of N-heterocyclic carbene (NHC)-coordinated ruthenium(II) arene complexes Ru1-Ru6 with the formula [Ru(p-cymene)(L)Cl]PF6 (L = NHC ligand with varying substituents). Cell-based in vitro studies revealed that despite the structural similarity, Ru1-Ru6 exhibited distinct cytotoxic activities against cancer cells. In particular, Ru4 and Ru6, which bear n-octyl and pentamethylbenzyl motifs, respectively, were the most active at inducing apoptosis. In human ovarian A2780 cancer cells, Ru4 and Ru6 showed the highest cytotoxicities with IC50 values of 2.74 ± 0.15 μM and 1.98 ± 0.10 μM, respectively, and they were approximately 2-fold more potent than cisplatin (IC50 = 5.55 ± 0.37 μM). In addition to the cell killing capacity, inhibition of cell migration was validated by using these two optimized complexes. Mechanistic studies revealed that Ru4 and Ru6 complexes induced apoptosis in a caspase-dependent manner, primarily through intracellular reactive oxygen species (ROS) overproduction and cell cycle arrest at G1 phase. Furthermore, in a preclinical metastatic model of A2780 tumor xenograft, administration...Continue Reading

Citations

Mar 24, 2021·Metallomics : Integrated Biometal Science·Bo ChuFupei Liang
May 27, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Durairaj GopalakrishnanMani Ganeshpandian
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Natalia MiklášováJán Mojžiš

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