Abstract
A number of analogues of combretastatin A-4 (1), containing a thiophene ring interposed between the two phenyl groups, have been prepared. The synthesis of these compounds employed a combination of palladium-mediated coupling and iodocyclization techniques. The thiophene compounds 11, 14, 18, and 19 also represent non-benzofused analogues of some recently described tubulin binding benzo[b]thiophenes 3-5. The most active thiophene compounds identified in this study were 11, 14, and 18. Overall they are less active than 1 but exhibit comparable activity to the most active of the benzo[b]thiophenes 3-5. A structure-activity relationship of these compounds is considered.
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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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / metabolism*
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Antineoplastic Agents / pharmacology
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Breast Neoplasms / drug therapy
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Colchicine / metabolism
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Colchicine / pharmacology
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Drug Screening Assays, Antitumor
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Guaiacol / analogs & derivatives
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Guaiacol / chemistry
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Guaiacol / metabolism
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Guaiacol / pharmacology
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Humans
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Stilbenes / chemistry
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Stilbenes / pharmacology*
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Structure-Activity Relationship
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Thiophenes / chemistry
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Thiophenes / metabolism
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Thiophenes / pharmacology
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Tubulin / drug effects
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Tubulin / metabolism*
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Tumor Cells, Cultured
Substances
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2-(3-hydroxy-4-methoxyphenyl)-3-((3,4,5-trimethoxyphenyl)carbonyl)thiophene
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2-(3-hydroxy-4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)thiophene
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Antineoplastic Agents
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Stilbenes
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Thiophenes
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Tubulin
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thiophene A
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Guaiacol
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fosbretabulin
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Colchicine