Highly cytotoxic and neurotoxic acetogenins of the Annonaceae: new putative biological targets of squamocin detected by activity-based protein profiling.
Acetogenins of the Annonaceae are strong inhibitors of mitochondrial complex I but discrepancies in the structure/activity relationships pled the search for other targets within the whole cell proteome. Combining hemisynthetic work, Cu-catalyzed Huisgen cycloaddition and proteomic techniques we have identified new putative protein targets of squamocin ruling out the previously accepted 'complex I dogma'. These results give new insights into the mechanism of action of these potent neurotoxic molecules.
Derbré
Séverine
S
Laboratoire de Pharmacognosie associé au CNRS, UMR 8076, Faculté de Pharmacie, Université Paris-Sud 11, Châtenay-Malabry Cedex, France.
Gil
Sophie
S
Taverna
Myriam
M
Boursier
Céline
C
Nicolas
Valérie
V
Demey-Thomas
Emmanuelle
E
Vinh
Joëlle
J
Susin
Santos A
SA
Hocquemiller
Reynald
R
Poupon
Erwan
E
D054378:Acetogenins / Q000494:pharmacology*; D029061:Annonaceae / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005663:Furans / Q000494:pharmacology*; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D054378:Acetogenins; D005663:Furans; D007783:Lactones; D011506:Proteins; C059660:squamocin