0000000000331602
AUTHOR
Raúl Aragón
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.
Specific interactions of monotetrahydrofuranic annonaceous acetogenins as inhibitors of mitochondrial complex I.
Annonaceous acetogenins (ACG) are a wide group of cytotoxic compounds isolated from plants of the Annonaceae family. Some of them are promising candidates to be a future new generation of antitumor drugs due to the ability to inhibit the NADH:ubiquinone oxidoreductase of the respiratory chain (mitochondrial complex I), main gate of the energy production in the cell. ACG are currently being tested on standard antitumor trials although little is known about the structure activity relationship at the molecular level. On recent studies, the relevance of several parts of the molecule for the inhibitory potency has been evaluated. Due to the great diversity of skeletons included in this family of…
Acetogenins from Annona glabra seeds
Abstract From the cytotoxic ethanol extract of Annona glabra seeds, a new mono-tetrahydrofuranic (mono-THF) acetogenin, glabranin, as well as pair of 22-epimer bis-THF acetogenins, were isolated by semipreparative HPLC. Four known mono-THF acetogenins with an identical threo/trans/threo relative configuration, annonacin, annonacinone, corossolin and corossolone, were found to be potent inhibitors of complex I of the mitochondrial respiratory chain.