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ID: ALA1134219

Journal: Bioorg Med Chem Lett

Title: Gamma-lactone-Functionalized antitumoral acetogenins are the most potent inhibitors of mitochondrial complex I.

Authors: Tormo JR, Estornell E, Gallardo T, González MC, Cavé A, Granell S, Cortes D, Zafra-Polo MC.

Abstract: To study the relevance of the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety of the antitumoral acetogenins of Annonaceae for potent mitochondrial complex I inhibition, we have prepared a series of semisynthetic acetogenins with modifications only in this part of the molecule, from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hydroxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural beta-hydroxy gamma-methyl gamma-lactone acetogenins, laherradurin (3) and itrabin (4), are more potent complex I inhibitors than any other known compounds.

CiteXplore: 11266168

DOI: 10.1016/s0960-894x(01)00036-1