Bisbenzyltetrahydroisoquinolines, a new class of inhibitors of the mitochondrial respiratory chain complex I.
Four bisbenzyltetrahydroisoquinoline alkaloids (-)-medelline, (+)-antioquine, (+)-aromoline, and (+)-obamegine were isolated from the fruits of Xylopia columbiana. These compounds, the previously isolated alkaloids (+)-thaligrisine and (+)-isotetrandrine, as well as their O-acetylated derivatives were assayed on submitochondrial particles from beef heart as inhibitors of the mammalian respiratory chain. The results revealed that these alkaloids act as selective inhibitors of mitochondrial complex I in a 0.15 - 4.71 microM range. O-Acetylation, which increases their lipophilicity, considerably increased the inhibitory potency.
Granell
Susana
S
Departamento de Farmacología, Laboratorio de Farmacognosia, Universidad de Valencia, Burjassot, Spain.
Andreu
Inmaculada
I
Martí
Daniel
D
Cavé
Adrién
A
Aragón
Raúl
R
Estornell
Ernesto
E
Cortes
Diego
D
Zafra-Polo
M Carmen
MC
D000818:Animals; D029061:Annonaceae; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002417:Cattle; D004579:Electron Transport / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D044182:Benzylisoquinolines; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D009247:NADH, NADPH Oxidoreductases