Abstract
The synthesis of new 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones is reported. The antitumor activity was evaluated according to the protocols available at the National Cancer Institute (NCI), Bethesda, MD. To investigate the mechanism of action of the most potent antitumor agent of this series, its effect on growth of HT-29 colon carcinoma cells was studied. Its ability to inhibit cellular proliferation was mediated by cell cycle arrest at the G2/M phase, accompanied by inhibition of ornithine decarboxylase (ODC), the limiting enzyme of polyamine synthesis, and followed by induction of apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Binding Sites / drug effects
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Cell Cycle / drug effects
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Cell Division / drug effects*
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Design
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Drug Screening Assays, Antitumor
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G2 Phase / drug effects*
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HT29 Cells
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry
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Indoles / pharmacology*
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Molecular Structure
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Ornithine Decarboxylase Inhibitors*
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Polyamines / metabolism
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Stereoisomerism
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Structure-Activity Relationship
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Thiadiazoles / chemical synthesis
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Thiadiazoles / chemistry
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Thiadiazoles / pharmacology*
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Thiazoles / chemical synthesis
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Thiazoles / chemistry
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Thiazoles / pharmacology*
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Indoles
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Ornithine Decarboxylase Inhibitors
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Polyamines
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Thiadiazoles
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Thiazoles