Organic letters, 2017-12, Vol.19 (24), p.6752-6755
2017
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Details
- Autor(en) / Beteiligte
- Titel
- Organocatalytic Asymmetric Synthesis of Spiro-oxindole Piperidine Derivatives That Reduce Cancer Cell Proliferation by Inhibiting MDM2–p53 Interaction
- Ist Teil von
- Organic letters, 2017-12, Vol.19 (24), p.6752-6755
- Ort / Verlag
- United States: American Chemical Society
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Asymmetric synthesis of pharmacologically interesting piperidine-fused spiro-oxindole derivatives has been achieved via an organocatalytic Michael/aza-Henry/hemiaminalization cascade reaction. Chiral compounds synthesized by this strategy potently inhibited the proliferation of several breast cancer cell lines. Mechanistic studies suggest that the most potent compound 9e can directly interfere with MDM2–p53 interactions and elevate protein levels of p53 and p21, thereby inducing cell cycle arrest and mitochondrial apoptosis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1523-7060eISSN: 1523-7052DOI: 10.1021/acs.orglett.7b03516Titel-ID: cdi_proquest_miscellaneous_1973460798
- Format
- –
- Schlagworte
- Antineoplastic Agents - chemical synthesis, Antineoplastic Agents - pharmacology, Apoptosis - drug effects, Binding Sites, Catalysis, Cell Proliferation - drug effects, Humans, MCF-7 Cells, Molecular Dynamics Simulation, Oxindoles - chemical synthesis, Oxindoles - pharmacology, Piperidines - chemical synthesis, Piperidines - pharmacology, Proto-Oncogene Proteins c-mdm2 - antagonists & inhibitors, Spiro Compounds - chemical synthesis, Spiro Compounds - pharmacology, Stereoisomerism, Tumor Suppressor Protein p53 - antagonists & inhibitors