Pyridinium and indole orientation determines the mitochondrial uncoupling and anti-cancer efficiency of F16

European Journal of Medicinal Chemistry
Juan XuYi Liu

Abstract

F16 is a mitochondria-targeted, broad-spectrum anticancer agent in the pre-clinic cancer therapy. Here we developed two fluorescent isomers of F16 (o-F16 and m-F16) with entirely different photophysical properties, uncoupling activity, and cytotoxicity by merely modifying the linking orientation of pyridinium and indole units. Individually, o-F16 acted as a strong uncoupler to reduce the mitochondrial respiration efficiency, while m-F16 could hardly uncouple the mitochondrial respiration due to its poor proton dissociation capability. Owing to their intrinsic fluorescence, o-F16 and m-F16 could specifically image mitochondria in the green and red channel, respectively. This work could provide useful information for the development of uncouplers and design of mitochondrial-targeted drugs.

Citations

Jul 23, 2020·Drug and Chemical Toxicology·Fümet Duygu ÜstündağEbru Emekli-Alturfan
Aug 8, 2021·International Journal of Molecular Sciences·Joseph E FriedlanderHui Feng
Sep 30, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jiang-Lin WangFeng-Lei Jiang

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