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ID: ALA1143445

Journal: Bioorg Med Chem Lett

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

Authors: Derbré S, Gil S, Taverna M, Boursier C, Nicolas V, Demey-Thomas E, Vinh J, Susin SA, Hocquemiller R, Poupon E.

Abstract: 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.

CiteXplore: 18851912

DOI: 10.1016/j.bmcl.2008.09.091