title: Selective action of acetogenin mitochondrial complex I inhibitors.
abstract: Five annonaceous acetogenins, rolliniastatin-1 [structure: see text], rolliniastatin-2 [structure: see text], laherradurin [structure: see text], squamocin [structure: see text], annonacin [structure: see text], and rotenone as a reference, differing in their NADH oxidase inhibition activity, have been evaluated for antifeedant, insecticidal, trypanocidal and cytotoxic effects on insect, mammalian and tumor cells. All the test compounds were toxic to Leptinotarsa decemlineata, demonstrated selective cytotoxicity to insect Sf9 cells and a panel of tumor cell lines with the multidrug-resistant SW480 (P-glycoprotein+, Pgp+) being the most sensitive one. Compounds [structure: see text] and rotenone had post-ingestive effects against Spodoptera littoralis larvae while [structure: see text] and rotenone were active against Trypanosoma cruzi. Based on their biochemical properties (inhibition of the mitochondrial NADH oxidase activity), the in vivo effects of these compounds on S. littoralis and their cytotoxic effects on Sf9 and tumor cells were more predictable than their effect on T. cruzi and mammalian cells.
authors.affiliation: Centro de Ciencias Medioambientales, CSIC, Serrano 115-dpdo., 28006 Madrid, Spain. azu@ccma.csic.es
authors.forename: Azucena
authors.initials: A
authors.lastname: González-Coloma
authors.forename: Ana
authors.initials: A
authors.lastname: Guadaño
authors.forename: Concepción
authors.initials: C
authors.lastname: de Inés
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez-Díaz
authors.forename: Diego
authors.initials: D
authors.lastname: Cortes
mesh_terms: D000818:Animals; D018533:Biomass; D016466:CHO Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003603:Cytotoxins / Q000302:isolation & purification / Q000494:pharmacology; D042967:Electron Transport Complex I; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D007313:Insecta / Q000254:growth & development; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D031045:Rollinia / Q000737:chemistry*; D012402:Rotenone / Q000494:pharmacology*; D018411:Spodoptera / Q000254:growth & development
chemical_list: D003603:Cytotoxins; D004791:Enzyme Inhibitors; D005663:Furans; D010936:Plant Extracts; D012402:Rotenone; C061022:bullatacin; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I