Abstract
A series of novel combretastatin A4 analogues, in which the cis-olefinic bridge is replaced by a cyclopropyl-vinyl or a cyclopropyl-amide moiety, were synthesized and evaluated for inhibition of tubulin polymerization and antiproliferative activity. The derivative 9a with a (cis,E)-cyclopropyl-vinyl unit is the most promising compound. As expected, molecular docking of 9a has shown that only one of the cis-cyclopropyl enantiomers is a good ligand for tubulin.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis*
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Amides / pharmacology
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Binding Sites / drug effects
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Cell Line, Tumor
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Cyclopropanes / chemical synthesis*
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Cyclopropanes / pharmacology
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Drug Evaluation, Preclinical / methods
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Humans
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Protein Binding / drug effects
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Stilbenes / chemical synthesis*
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Stilbenes / pharmacology
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Tubulin / metabolism
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Vinyl Compounds / chemical synthesis*
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Vinyl Compounds / pharmacology
Substances
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Amides
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Cyclopropanes
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Stilbenes
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Tubulin
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Vinyl Compounds
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fosbretabulin