Synthesis and inhibitory activity of ubiquinone-acetogenin hybrid inhibitor with bovine mitochondrial complex I.
To elucidate the inhibitory action of acetogenins, the most potent inhibitors of mitochondrial complex I, we synthesized an acetogenin analogue which possesses a ubiquinone ring (i.e., the physiological substrate of complex I) in place of the alpha,beta-unsaturated gamma-lactone ring of natural acetogenins, and named it Q-acetogenin. Our results indicate that the gamma-lactone ring of acetogenins is completely substitutable with the ubiquinone ring. This fact is discussed in light of the inhibitory action of acetogenins.
Yabunaka
Hiromi
H
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, 606-8502, Kyoto, Japan.
Abe
Masato
M
Kenmochi
Atsushi
A
Hamada
Takeshi
T
Nishioka
Takaaki
T
Miyoshi
Hideto
H
D054378:Acetogenins; D000818:Animals; D002417:Cattle; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
D054378:Acetogenins; D005663:Furans; D007202:Indicators and Reagents; C481418:Q-acetogenin; D014451:Ubiquinone; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I