Abstract
A series of compounds designed to adopt a conformation similar to the tubulin-binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open-chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling β-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open-chain analogs showed moderate to good cytotoxicity.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Antineoplastic Agents, Phytogenic / chemical synthesis
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Antineoplastic Agents, Phytogenic / chemistry*
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Antineoplastic Agents, Phytogenic / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Crystallography, X-Ray
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Drug Design
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Humans
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Models, Molecular
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Molecular Conformation
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Neoplasms / drug therapy
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Paclitaxel / analogs & derivatives*
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Paclitaxel / chemical synthesis
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Paclitaxel / chemistry
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Paclitaxel / pharmacology*
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Tubulin / metabolism
Substances
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Antineoplastic Agents, Phytogenic
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Tubulin
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Paclitaxel