1. The potent protein phosphatase 2A inhibitors aminocytostatins: new derivatives of cytostatin
- Author
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Shigehiro Tohyama, Masayuki Igarashi, Kazuaki Matoba, Ryuichi Sawa, Hiroyuki Inoue, Hideyuki Muramatsu, Manabu Kawada, and Masaki Hatano
- Subjects
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 - Abstract
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.
- Published
- 2021