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Updated: Apr 24, 2026

Analyzing Supercomplexes of the Mitochondrial Electron Transport Chain with Native Electrophoresis, In-gel Assays, and Electroelution
Published on: June 1, 2017
The structure-activity relationships of mono-THF ACGs on mitochondrial complex I with a molecular modelling study
Yun-Jie Miao1, Xiao-Fang Xu, Fei Xu
1a Nanjing University of Chinese Medicine, Pharmaceutical Institute , Nanjing 210046 , P.R. China.
Abstract:
Annonaceous acetogenins (ACGs) are one of the most powerful groups of mitochondrial complex I inhibitors. In this study, 24 ACGs with different chemical structures have been tested against mitochondrial complex I isolated in our laboratory. Molecular modelling study of the six mono-tetrahydrofuran (THF) ACGs in these 24 compounds has been performed to investigate the relationship between their inhibitory activity and chemical structures. IC50 of every ACGs against mitochondrial complex I was determined with a micro plate reader. The results show that every ACG can inhibit mitochondrial complex I and the six mono-THF ACGs' activities are in agreement with their molecular modelling results. It is suggested that proper length and flexibility of the alkyl spacer moiety, which links the THF and the α,β-unsaturated Q-lactone ring moieties, are essential for the potent activity. Both the number of hydroxyl groups and stereochemical structures of mono-THF ACGs impact the activity.
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