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Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analogues
Authors:Wender Paul A  Jankowski Orion D  Longcore Kate  Tabet Elie A  Seto Haruo  Tomikawa Taijiro
Institution:Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. wenderp@stanford.edu
Abstract:structure: see text] Apoptolidin (1) exhibits potent and highly selective apoptosis inducing activity against sensitive cancer cell lines and is hypothesized to act by inhibition of mitochondrial F(0)F(1)-ATP synthase. A series of apoptolidin derivatives, including a new intermolecular Diels-Alder adduct, were analyzed for antiproliferative activity in E1A-transformed rat fibroblasts. Potent F(0)F(1)-ATPase inhibition was not a sufficient determinant of antiproliferative activity for several analogues, suggesting the existence of a secondary biological target or more complex mode of action for apoptolidin.
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