Necroptosis-Inducing Rhenium(V) Oxo Complexes
Journal of the American Chemical Society2015Vol. 137(8), pp. 2967–2974
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Kogularamanan Suntharalingam, Samuel G. Awuah, Peter M. Bruno, Timothy C. Johnstone, Fang Wang, Lin Wei, Yao‐Rong Zheng, Julia E. Page, Michael T. Hemann, Stephen J. Lippard
Abstract
Rhenium(V) oxo complexes of general formula [ReO(OMe)(N^N)Cl2], 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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