title: Tucumanin, a beta-hydroxy-gamma-lactone bistetrahydrofuranic acetogenin from Annona cherimolia, is a potent inhibitor of mitochondrial complex I.
abstract: A new beta-hydroxy-gamma-methyl-gamma-lactone bistetrahydrofuranic acetogenin, tucumanin, with the infrequent symmetrical threo/trans/threo/trans/threo relative configuration at the tetrahydrofuran rings was isolated from Annona cherimolia (Annonaceae) seeds. The inhibitory potency on the mitochondrial complex I of acetogenins with this relative configuration (tucumanin and asimicin)was compared with that shown by the corresponding pairs with an asymmetrical threo/trans/threo/trans/erythro relative configuration (laherradurin/rolliniastatin-2, and itrabin/molvizarin). All these compounds act as selective inhibitors of mitochondrial complex I in the 0.18 - 1.55 nM range.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Avenida Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Barrachina
authors.forename: Adriana
authors.initials: A
authors.lastname: Neske
authors.forename: Susana
authors.initials: S
authors.lastname: Granell
authors.forename: Almudena
authors.initials: A
authors.lastname: Bermejo
authors.forename: Nadia
authors.initials: N
authors.lastname: Chahboune
authors.forename: Noureddine
authors.initials: N
authors.lastname: El Aouad
authors.forename: Olga
authors.initials: O
authors.lastname: Alvarez
authors.forename: Alicia
authors.initials: A
authors.lastname: Bardon
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Zafra-Polo
mesh_terms: D031041:Annona; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005663:Furans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012639:Seeds
chemical_list: D004791:Enzyme Inhibitors; D005663:Furans; D007783:Lactones; D010936:Plant Extracts; C493766:tucumanin; D042967:Electron Transport Complex I