6533b7d9fe1ef96bd126b994
RESEARCH PRODUCT
Bisbenzyltetrahydroisoquinolines, a New Class of Inhibitors of the Mitochondrial Respiratory Chain Complex I
M. Carmen Zafra-poloAdrien CavéRaúl AragónImmaculada AndreuSusana GranellDiego CortesErnesto EstornellDaniel Martísubject
StereochemistryRespiratory chainAnnonaceaePharmaceutical ScienceBiologyBenzylisoquinolinesMitochondria HeartAnalytical Chemistrylaw.inventionElectron TransportInhibitory Concentration 50lawDrug DiscoveryAnimalsNADH NADPH Oxidoreductasesheterocyclic compoundsMitochondrial respiratory chain complex ISubmitochondrial particleEnzyme InhibitorsPharmacologyPlant ExtractsOrganic Chemistrybiology.organism_classificationElectron transport chainComplementary and alternative medicineBiochemistryAnnonaceaeLipophilicityMolecular MedicineCattlePhytotherapyXylopiaPhytotherapydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2004-04-29 | Planta Medica |