Abstract
[reaction: see text] The syntheses of five laulimalide analogues are described, incorporating modifications at the C(16)-C(17)-epoxide, the C(20)-alcohol, as well as the C(1)-C(3)-enoate of the parent natural product. The resultant analogues are active in drug-sensitive HeLa and MDA-MB-435 cell lines. Significantly, like laulimalide, these analogues are poor substrates for the drug transport protein P-glycoprotein (Pgp) and are thus effective against Taxol-resistant cell lines.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor / drug effects
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Drug Resistance, Neoplasm
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Drug Screening Assays, Antitumor
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Epoxy Compounds / chemistry
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HeLa Cells / drug effects
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Humans
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Macrolides
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Molecular Structure
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Stereoisomerism
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Taxoids / chemical synthesis*
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Taxoids / metabolism
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Taxoids / pharmacology
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antineoplastic Agents
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Epoxy Compounds
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Macrolides
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Taxoids
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laulimalide