Necroptosis Induced by Ruthenium(II) Complexes as Dual Catalytic Inhibitors of Topoisomerase I/II.

Angewandte Chemie
Kai XiongHui Chao

Abstract

Inducing necroptosis in cancer cells is an effective approach to circumvent drug-resistance. Metal-based triggers have, however, rarely been reported. Ruthenium(II) complexes containing 1,1-(pyrazin-2-yl)pyreno[4,5-e][1,2,4]triazine were developed with a series of different ancillary ligands (Ru1-7). The combination of the main ligand with bipyridyl and phenylpyridyl ligands endows Ru7 with superior nucleus-targeting properties. As a rare dual catalytic inhibitor, Ru7 effectively inhibits the endogenous activities of topoisomerase (topo) I and II and kills cancer cells by necroptosis. The cell signaling pathway from topo inhibition to necroptosis was elucidated. Furthermore, Ru7 displays significant antitumor activity against drug-resistant cancer cells in vivo. To the best of our knowledge, Ru7 is the first Ru-based necroptosis-inducing chemotherapeutic agent.

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Citations

Sep 18, 2020·Chemical Communications : Chem Comm·Zizhuo ZhaoJinquan Wang
Dec 11, 2020·Drug Design, Development and Therapy·Sang Yeul LeeTae-Gyu Nam
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Luna SongHongfei Wang
Jun 15, 2021·Chemical Science·Elizabeth J AnthonyZijin Zhang
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Qi SunQianling Zhang
Jan 7, 2022·Dalton Transactions : an International Journal of Inorganic Chemistry·Yun-Qiong GuHong Liang

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