Abstract
In the present manuscript, starting from the 1,4-benzodiazepin-2-one nucleus, a privileged structure in medicinal chemistry, we have synthesized a novel class of cis-locked combretastatins named combreatabenzodiazepines. They show similar cytotoxic and antitubulin activity compared to combretastatin A-4 in neuroblastoma cells, showing a better pharmacokinetic profile. This class of compounds has therefore the potential for further development as antitubulin agents.
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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Benzodiazepinones / chemical synthesis
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Benzodiazepinones / chemistry
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Benzodiazepinones / pharmacology*
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Cell Proliferation / drug effects
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Crystallography, X-Ray
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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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Humans
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Models, Molecular
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Molecular Structure
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Structure-Activity Relationship
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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*
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Benzodiazepinones
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Tubulin
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Tubulin Modulators