Bisbenzyltetrahydroisoquinolines, a New Class of Inhibitors of the Mitochondrial Respiratory Chain Complex I

Abstract

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 μM range. O-Acetylation, which increases their lipophilicity, considerably increased the inhibitory potency.

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