Inhibitory effects on mitochondrial complex I of semisynthetic mono-tetrahydrofuran acetogenin derivatives.
Modifications in the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety or in the alkyl chain that links this terminal gamma-lactone with the alpha,alpha'-dihydroxylated THF system of the natural mono-tetrahydrofuranic acetogenins, annonacin and annonacinone, led to the preparation of eight semisynthetic derivatives. Their inhibitory effects on mitochondrial complex I is discussed and compared with that of the classical complex I inhibitor, rotenone.
Departamento de Farmacología, Laboratorio de Farmacognosia, Facultad de Farmacia, Universidad de Valencia, Avda. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
José R
JR
Tormo
Teresa
T
Gallardo
Eva
E
Peris
Almudena
A
Bermejo
Nuria
N
Cabedo
Ernesto
E
Estornell
M Carmen
MC
Zafra-Polo
Diego
D
Cortes
D054378:Acetogenins; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000138:chemical synthesis* / Q000494:pharmacology*; D005663:Furans / Q000138:chemical synthesis / Q000494:pharmacology; D007700:Kinetics; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors
D054378:Acetogenins; D004791:Enzyme Inhibitors; D005233:Fatty Alcohols; D005663:Furans; D007783:Lactones; D009097:Multienzyme Complexes; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I