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Bioorg Med Chem Lett. 2008 Nov 1;18(21):5741-4. doi: 10.1016/j.bmcl.2008.09.091. Epub 2008 Sep 30.

Highly cytotoxic and neurotoxic acetogenins of the Annonaceae: new putative biological targets of squamocin detected by activity-based protein profiling.

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  • 1Laboratoire de Pharmacognosie associé au CNRS, UMR 8076, Faculté de Pharmacie, Université Paris-Sud 11, Châtenay-Malabry Cedex, France.


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.

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