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A new diketopiperazine-like inhibitor of bone morphogenetic protein-induced osteoblastic differentiation produced by marine-derived Aspergillus sp. BFM-0085

The Journal of Antibiotics volume 73, pages 554–558 (2020)Cite this article

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Abstract

A new diketopiperazine-like compound, designated protuboxepin K (1), was isolated together with the known structurally related protuboxepin A (2) from culture broth of the marine-derived fungal strain Aspergillus sp. BFM-0085 isolated from a sediment sample of Tokyo Bay. The structure of protuboxepin K was elucidated by spectroscopic data, including 1D and 2D NMR. Compounds 1 and 2 inhibited bone morphogenetic protein (BMP)-induced alkaline phosphatase activity with IC50 values of 4.7 and 25.2 μM, respectively, in mutant BMP receptor-carrying C2C12(R206H) cells.

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Acknowledgements

We thank Ms. Noriko Sato and Dr. Kenichiro Nagai (School of Pharmaceutical Sciences, Kitasato University) for measurements of NMR spectra and MS data, and Mr. Seiji Taki (Tokyo University of Marine Science and Technology) for collecting sediment samples of Tokyo Bay. This work was supported by JSPS KAKENHI Grant number JP26253009 (HT), the Takeda Science Foundation (HT), and a Kitasato University Research Grant for Young Researchers (SO).

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Authors and Affiliations

  1. Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Satoshi Ohte, Nobuhiro Koyama & Hiroshi Tomoda

  2. Department of Microbial Chemistry, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Satoshi Ohte, Takehiro Shiokawa, Nobuhiro Koyama & Hiroshi Tomoda

  3. Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Satoshi Ohte, Nobuhiro Koyama & Hiroshi Tomoda

  4. Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1241, Japan

    Takenobu Katagiri

  5. Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, 4-5-7, Konan, Minato-ku, Tokyo, 108-8477, Japan

    Chiaki Imada

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  1. Satoshi Ohte
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  2. Takehiro Shiokawa
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  4. Takenobu Katagiri
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Correspondence to Hiroshi Tomoda.

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This article is dedicated to Professor William Fenical in recognition of his contributions to marine-derived secondary metabolites.

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41429_2020_316_MOESM1_ESM.pdf

A new diketopiperazine-like inhibitor of bone morphogenetic protein-induced osteoblastic differentiation produced by marine-derived <i>Aspergillus</i> sp. BFM-0085

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Ohte, S., Shiokawa, T., Koyama, N. et al. A new diketopiperazine-like inhibitor of bone morphogenetic protein-induced osteoblastic differentiation produced by marine-derived Aspergillus sp. BFM-0085. J Antibiot 73, 554–558 (2020). https://doi.org/10.1038/s41429-020-0316-3

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