Substituted alpha-(phenylhydrazono)phenylacetonitrile derivatives. Part 1: A new class of uncoupler of oxidative phosphorylation.
Substituted alpha-(phenylhydrazono)phenylacetonitrile derivatives have been discovered which constitute a series of potent uncouplers of oxidative phosphorylation. Systematic variation of substituents on both benzene rings has clearly demonstrated the importance of steric congestion around the ionisation site and delocalisation of negative charge in the anionic form. Replacement of the cyano group by other electron-withdrawing groups leads to a dramatic decrease in uncoupling activity. The sub-nanomolar levels of uncoupling activity found in certain members indicate that these compounds are the most potent uncouplers yet reported.
Danko
Peter
P
Synkola Consortium, Mlynska Dolina, 84215 Bratislava, Slovakia.
Flury
Thomas
T
Hall
Roger G
RG
Karrer
Friedrich
F
Kienast
Heinz
H
Kriz
Miroslav
M
Leuenberger
Katrin
K
Pascual
Alfons
A
Steiger
Arthur
A
Trah
Stephan
S
D000818:Animals; D004175:Diptera / Q000187:drug effects; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects; D015394:Molecular Structure; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014475:Uncoupling Agents / Q000737:chemistry* / Q000494:pharmacology
D014475:Uncoupling Agents