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The potent protein phosphatase 2A inhibitors aminocytostatins: new derivatives of cytostatin

The Journal of Antibiotics volume 74, pages 743–751 (2021)Cite this article

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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.

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Acknowledgements

We are grateful to Dr. K. Iijima, Ms. Y. Takahashi, and Ms. Y. Kubota (Microbial Chemistry Research Center) for the MS and NMR measurements. We also thank Ms. C. Hayashi for the bioassays.

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Authors and Affiliations

  1. Institute of Microbial Chemistry, Microbial Chemistry Research Foundation (BIKAKEN), Shinagawa-ku, Tokyo, Japan

    Shigehiro Tohyama, Manabu Kawada, Hideyuki Muramatsu, Masaki Hatano, Hiroyuki Inoue, Kazuaki Matoba, Ryuichi Sawa & Masayuki Igarashi

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  1. Shigehiro Tohyama
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  2. Manabu Kawada
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  3. Hideyuki Muramatsu
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  4. Masaki Hatano
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  6. Kazuaki Matoba
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  7. Ryuichi Sawa
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  8. Masayuki Igarashi
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Correspondence to Shigehiro Tohyama.

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Tohyama, S., Kawada, M., Muramatsu, H. et al. The potent protein phosphatase 2A inhibitors aminocytostatins: new derivatives of cytostatin. J Antibiot 74, 743–751 (2021). https://doi.org/10.1038/s41429-021-00455-w

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  • DOI: https://doi.org/10.1038/s41429-021-00455-w

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