Indole-TEMPO conjugates alleviate ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function

Publication date: Available online 19 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Wei Bi, Yue Bi, Xiang Gao, Pengfei Li, Shanshan Hou, Yanrong Zhang, Cathy Bammert, Steffen Jockusch, Thomas D. Legalley, K. Michael Gibson, Lanrong Bi
Mitochondrial oxidative damage contributes to a wide range of pathologies including ischemia/ reperfusion injury. Accordingly, protecting mitochondria from oxidative damage should possess therapeutic relevance. In the present study, we have designed and synthesized a series of novel indole-TEMPO conjugates that manifested good anti-inflammatory properties in a murine model of xylene-induced ear edema. We have demonstrated that these compounds can protect cells from simulated ischemia/reperfusion (s-I/R)-induced reactive oxygen species (ROS) overproduction and mitochondrial dysfunction. Furthermore, we have demonstrated that indole-TEMPO conjugates can attenuate organ damage induced in rodents via intestinal I/R injury. We therefore propose that the pharmacological profile and mechanism of action of these indole-TEMPO conjugates involve convergent roles, including the ability to decrease free radical production via lipid peroxidation which couples to an associated decrease in ROS-mediated activation of the inflammatory process. We further hypothesize that the protective effects of indole-TEMPO conjugates partially reside in maintaining optimal mitochondrial function.

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