6533b82afe1ef96bd128cc9a
RESEARCH PRODUCT
Gamma-lactone-Functionalized antitumoral acetogenins are the most potent inhibitors of mitochondrial complex I.
Susana GranellTeresa GallardoAdrien CavéM. Carmen Zafra-poloDiego CortesErnesto EstornellM. Carmen GonzálezJosé R. Tormosubject
StereochemistryClinical BiochemistrySubmitochondrial ParticlesPharmaceutical ScienceAntineoplastic AgentsMitochondrionBiochemistryMitochondria HeartLactonesMagnoliopsidaMultienzyme ComplexesDrug DiscoveryMoietyAnimalsNADH NADPH OxidoreductasesFuransMolecular Biologychemistry.chemical_classificationElectron Transport Complex IbiologyMolecular StructureOrganic ChemistryBiological activitybiology.organism_classificationIn vitroEnzymechemistryEnzyme inhibitorAnnonaceaebiology.proteinMolecular MedicineCattleLactonedescription
To study the relevance of the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety of the antitumoral acetogenins of Annonaceae for potent mitochondrial complex I inhibition, we have prepared a series of semisynthetic acetogenins with modifications only in this part of the molecule, from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hydroxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural beta-hydroxy gamma-methyl gamma-lactone acetogenins, laherradurin (3) and itrabin (4), are more potent complex I inhibitors than any other known compounds.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2001-03-01 | Bioorganicmedicinal chemistry letters |