Necroptosis-Inducing Rhenium(V) Oxo Complexes

作者：Suntharalingam Kogularamanan; Awuah Samuel G; Bruno Peter M; Johnstone Timothy C; Wang Fang; Lin Wei; Zheng Yao Rong; Page Julia E; Hemann Michael T; Lippard Stephen J^*

来源：Journal of the American Chemical Society, 2015, 137(8): 2967-2974.

DOI：10.1021/ja511978y

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.

• 出版日期2015-3-4