Structural investigations on the mitochondrial uncouplers niclosamide and FCCP

Ng, Mei Ying, Song, Zhi Jian, Tan, Choon Hong, Bassetto, Marcella and Hagen, Thilo 2024. Structural investigations on the mitochondrial uncouplers niclosamide and FCCP. FEBS Open Bio 14 (7) , pp. 1057-1071. 10.1002/2211-5463.13817

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/
Publisher:	Wiley Open Access
ISSN:	2211-5463
Date of First Compliant Deposit:	17 May 2024
Date of Acceptance:	2 May 2024
Last Modified:	19 Jul 2024 14:06
URI:	https://orca.cardiff.ac.uk/id/eprint/168997

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