Bioorganic & medicinal chemistry, 2017-10, Vol.25 (20), p.5268-5277
2017
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Details
- Autor(en) / Beteiligte
- Titel
- Design, synthesis and biological evaluation of novel antitumor spirotetrahydrothiopyran–oxindole derivatives as potent p53-MDM2 inhibitors
- Ist Teil von
- Bioorganic & medicinal chemistry, 2017-10, Vol.25 (20), p.5268-5277
- Ort / Verlag
- England: Elsevier Ltd
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- [Display omitted] p53–MDM2 protein-protein interaction is a promising target for novel antitumor drug development. Previously, we identified a new class of spirotetrahydrothiopyran–oxindole p53–MDM2 inhibitors by novel organocatalytic enantioselective cascade reactions. Herein, a series of new derivatives were designed, synthesized and assayed to investigate the structure-activity relationships. Among them, compound B14 bearing a novel spiroindole–thiopyranopyridone scaffold exhibited potent MDM2 inhibitory activity as well as antitumor activity, which could effectively induce the apoptosis of A549 cancer cells. It represents a promising lead compound for the development of novel antitumor agents.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0968-0896eISSN: 1464-3391DOI: 10.1016/j.bmc.2017.07.049Titel-ID: cdi_proquest_miscellaneous_1928510337
- Format
- –
- Schlagworte
- Antineoplastic Agents - chemical synthesis, Antineoplastic Agents - chemistry, Antineoplastic Agents - pharmacology, Antitumor activity, Apoptosis - drug effects, Cell Proliferation - drug effects, Dose-Response Relationship, Drug, Drug Design, Drug Screening Assays, Antitumor, Fluorescence Polarization, Humans, Indoles - chemistry, Indoles - pharmacology, Molecular Structure, Organocatalytic cascade reaction, p53–MDM2 inhibitors, Proto-Oncogene Proteins c-mdm2 - antagonists & inhibitors, Pyrans - chemistry, Pyrans - pharmacology, Spiro Compounds - chemistry, Spiro Compounds - pharmacology, Spirooxindole, Structure-Activity Relationship, Tumor Cells, Cultured, Tumor Suppressor Protein p53 - antagonists & inhibitors