期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 137, 期 8, 页码 2967-2974出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja511978y
关键词
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资金
- NCI [CA034992]
- NATIONAL CANCER INSTITUTE [R01CA034992, R37CA034992] Funding Source: NIH RePORTER
Rhenium(V) oxo complexes of general formula [ReO(OMe)(N<^>N)Cl-2], where N<^>N = 4,7-diphenyl-1,10-phenanthroline, 1, or 3,4,7,8-tetramethyl-1,10-phenanthroline, 2, effectively kill cancer cells by triggering necroptosis, a non-apoptotic form of cell death. Both complexes evoke necrosome (RIP1-RIP3)-dependent intracellular reactive oxygen species (ROS) production and propidium iodide uptake. The complexes also induce mitochondrial membrane potential depletion, a possible downstream effect of ROS production. Apparently, 1 and 2 are the first rhenium complexes to evoke cellular events consistent with programmed necrosis in cancer cells. Furthermore, 1 and 2 display low acute toxicity in C57BL/6 mice and reasonable stability in fresh human blood.
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