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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents* / chemical synthesis
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Antineoplastic Agents* / chemistry
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Antineoplastic Agents* / pharmacology
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Apoptosis / drug effects
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Drug Screening Assays, Antitumor
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Fibroblasts / drug effects
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Macrolides* / chemical synthesis
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Macrolides* / chemistry
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Macrolides* / pharmacology
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Models, Molecular
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Molecular Structure
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Proton-Translocating ATPases / antagonists & inhibitors*
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Rats
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Tumor Cells, Cultured
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Yeasts / enzymology
Substances
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Antineoplastic Agents
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Macrolides
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Proton-Translocating ATPases
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apoptolidin