Abstract
Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
MeSH terms
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Animals
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Antimitotic Agents / chemical synthesis*
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Antimitotic Agents / chemistry
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Antimitotic Agents / pharmacology
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Binding Sites
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Cell Cycle / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Colchicine / metabolism
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Drug Screening Assays, Antitumor
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Humans
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Mice
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Protein Binding
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Radioligand Assay
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Structure-Activity Relationship
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Thiophenes / chemical synthesis*
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Thiophenes / chemistry
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Thiophenes / pharmacology
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Tubulin / metabolism
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Tubulin Modulators / chemical synthesis
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Tubulin Modulators / chemistry
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Tubulin Modulators / pharmacology
Substances
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2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo(b)thiophene
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Antimitotic Agents
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Thiophenes
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Tubulin
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Tubulin Modulators
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Colchicine