Remarkable substituent effect: beta-aminosquamocin, a potent dual inhibitor of mitochondrial complexes I and III.
The introduction of a primary amine function on the terminal alpha,beta-unsaturated lactone of squamocin 1, a common structural hallmark of annonaceous acetogenins, shifted this specific inhibitor of mitochondrial complex I into a potent dual inhibitor of complexes I and III. The mechanism of action of beta-aminosquamocin 2, against these two respiratory targets, is studied and discussed in view of current structure-activity relationship knowledge in the acetogenin series.
Duval
Romain A
RA
Laboratoire de Pharmacognosie associé au CNRS (UMR 8076, BioCIS), Centre d'Etudes Pharmaceutiques, Université Paris-Sud 11, 92296 Châtenay-Malabry CEDEX, France.
Poupon
Erwan
E
Brandt
Ulrich
U
Hocquemiller
Reynald
R
D029061:Annonaceae / Q000737:chemistry*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors*; D005663:Furans / Q000737:chemistry* / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D005663:Furans; D007783:Lactones; C059660:squamocin; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III