New 4-hydroxypyridine and 4-hydroxyquinoline derivatives as inhibitors of NADH-ubiquinone reductase in the respiratory chain.
Many derivatives of 2,3-dimethoxy-4-hydroxypyridine, which were designed from examination of the structure-activity relationship of piericidins, were tested for inhibition of NADH-UQ reductase. The lipophilic side chain of those compounds was indicated to be a key part for activity and its optimal length was conjectured. By the use of two different phases of assay material, intact mitochondria and submitochondria, the size of a membrane effect was shown to depend on the structure of the side chain. 4-Hydroxyquinoline derivatives were also tested for an analogous role in relation to the electron transport function of menaquinone, and they were proven to be inhibitors of NADH-UQ reductase as good as the pyridine derivatives.
Chung
K H
KH
Korea Research Institute of Chemical Technology, Daejeon.
Cho
K Y
KY
Asami
Y
Y
Takahashi
N
N
Yoshida
S
S
D000818:Animals; D002417:Cattle; D004579:Electron Transport / Q000187:drug effects; D006912:Hydroxyquinolines / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone); D010101:Oxygen Consumption / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011808:Quinone Reductases / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism*
D006912:Hydroxyquinolines; D011725:Pyridines; C014047:hydroxypyridines; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases