Necroptosis Induced by Ruthenium(II) Complexes as Dual Catalytic Inhibitors of Topoisomerase I/II
| Autor: | Liting He, Jian Wan, Hui Chao, Thomas W. Rees, Yi-Xian Yuan, Liang-Nian Ji, Chen Qian, Lin Wei, Yu Chen, Kai Xiong, Xinxing Liao |
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| Rok vydání: | 2020 |
| Předmět: |
Metals in medicine
Topoisomerase Inhibitors Stereochemistry Necroptosis chemistry.chemical_element 010402 general chemistry 01 natural sciences Ruthenium Catalysis Cell Line Mice chemistry.chemical_compound Coordination Complexes In vivo Animals Humans Poly-ADP-Ribose Binding Proteins Cell Proliferation Triazine Cell Death Molecular Structure biology 010405 organic chemistry Chemistry Ligand Topoisomerase General Medicine Neoplasms Experimental General Chemistry 0104 chemical sciences DNA Topoisomerases Type II DNA Topoisomerases Type I Cancer cell Biocatalysis biology.protein |
| Zdroj: | Angewandte Chemie International Edition. 59:16631-16637 |
| ISSN: | 1521-3773 1433-7851 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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