The potent protein phosphatase 2A inhibitors aminocytostatins: new derivatives of cytostatin
| Autor: | Shigehiro Tohyama, Masayuki Igarashi, Kazuaki Matoba, Ryuichi Sawa, Hiroyuki Inoue, Hideyuki Muramatsu, Manabu Kawada, Masaki Hatano |
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| Rok vydání: | 2021 |
| Předmět: |
Cell Survival
Protein Conformation Streptomycetaceae Antineoplastic Agents Inhibitory postsynaptic potential Mice Structure-Activity Relationship Cytostatin In vivo Cell Line Tumor Drug Discovery Animals Moiety Protein Phosphatase 2 Pharmacology chemistry.chemical_classification Molecular Structure Chemistry Protein phosphatase 2 Organophosphates In vitro Molecular Docking Simulation Biochemistry Pyrones Docking (molecular) Lactone Protein Binding |
| Zdroj: | The Journal of Antibiotics. 74:743-751 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.1038/s41429-021-00455-w |
| Popis: | Specific inhibitors of protein phosphatase 2A (PP2A) mediate anticancer effects by augmenting the tumor-killing activity of natural killer (NK) cells. In this study, new PP2A inhibitors, aminocytostatins A-E, were isolated from Kitasatospora sp. MJ654-NF4 and structurally characterized. Aminocytostatins are derivatives of cytostatin, which is a specific PP2A inhibitor isolated from the same organism, and aminocytostatins have a characteristic amino group within the lactone moiety. Compared to cytostatin, aminocytostatin A showed a stronger inhibitory activity against PP2A in vitro and augmented the tumor-killing activity of NK cells in vivo. Furthermore, a docking model was generated to demonstrate the favorable activities of aminocytostatin A. |
| Databáze: | OpenAIRE |
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