Abstract
The enantioselective preparation of pharmacologically interesting chroman-fused spirooxindole derivatives is described based on an organocatalytic multicomponent cascade reaction. The compounds synthesized using this method potently inhibited the proliferation of various cancer cell lines. The most potent compound (7e) induced caspase-independent apoptosis and cell cycle arrest in MCF-7 breast cancer cells by interfering with the p53-MDM2 interaction and downstream pathways.
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 / metabolism
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Catalysis
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Cell Cycle Checkpoints / drug effects
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Cell Proliferation / drug effects
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Chemistry Techniques, Synthetic
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Chromans / chemical synthesis
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Chromans / chemistry*
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Chromans / metabolism
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Chromans / pharmacology*
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Humans
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Indoles / chemistry*
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MCF-7 Cells
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Models, Molecular
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Protein Conformation
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Proto-Oncogene Proteins c-mdm2 / chemistry
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Proto-Oncogene Proteins c-mdm2 / metabolism
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Tumor Suppressor Protein p53 / metabolism
Substances
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Antineoplastic Agents
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Chromans
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Indoles
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Tumor Suppressor Protein p53
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Proto-Oncogene Proteins c-mdm2