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- Title
Structural investigations on the mitochondrial uncouplers niclosamide and FCCP.
- Authors
Ng, Mei Ying; Song, Zhi Jian; Tan, Choon Hong; Bassetto, Marcella; Hagen, Thilo
- Abstract
There has been renewed interest in using mitochondrial uncoupler compounds such as niclosamide and carbonyl cyanide p‐(trifluoromethoxy)phenylhydrazone (FCCP) for the treatment of obesity, hepatosteatosis and diseases where oxidative stress plays a role. However, both FCCP and niclosamide have undesirable effects that are not due to mitochondrial uncoupling, such as inhibition of mitochondrial oxygen consumption by FCCP and induction of DNA damage by niclosamide. Through structure–activity analysis, we identified FCCP analogues that do not inhibit mitochondrial oxygen consumption but still provided good, although less potent, uncoupling activity. We also characterized the functional role of the niclosamide 4′‐nitro group, the phenolic hydroxy group and the anilide amino group in mediating uncoupling activity. Our structural investigations provide important information that will aid further drug development.
- Subjects
MITOCHONDRIA; AMINO group; OXYGEN consumption; DNA damage; DRUG development; OXIDATIVE stress
- Publication
FEBS Open Bio, 2024, Vol 14, Issue 7, p1057
- ISSN
2211-5463
- Publication type
Article
- DOI
10.1002/2211-5463.13817