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Isolation and structure determination of streptospherins B–F, novel cancer stem cell inhibitors, produced by Streptomyces sp. KUSC-240

The Journal of Antibiotics volume 78, pages 535–541 (2025)Cite this article

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Abstract

Streptospherin A (1), which has pentasubstituted benzene and tetrahydropyran moieties, was recently isolated in our laboratory from Streptomyces sp. KUSC-240 as a novel inhibitor of cancer stem cell (CSC) sphere formation. Given the potential of CSCs as target for cancer therapy because of their high malignancy, identification of CSC inhibitors is urgently needed. The chemical structure and biological activity of 1 prompted us to isolate other derivatives from Streptomyces sp. KUSC-240, leading here to the identification of new streptospherins B–F (2–6). Their planar structures were determined by HR-ESI-MS and NMR analyses. The absolute configuration of 4 was proposed by using a modified Mosher’s method, acetonide formation, and the J-based configuration analysis (JBCA) method. The absolute configurations of 3 and 5 were also determined by using ECD spectra and comparison with that of 4. Analysis of the whole genome sequence of the producing strain suggested a plausible biosynthesis pathway for 3–5. Compounds 2–6 inhibited CSC sphere formation and suppressed CSC growth, indicating that streptospherins are promising seed compounds for CSC inhibitors for cancer chemotherapy.

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Acknowledgements

This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [grant numbers 17H06401 (HK and MI), 19H02840, 22H04901, 23H04882, 24H00493 (all awarded to HK), and 23K13896 (HI)], the Project for Promotion of Cancer Research and Therapeutic Evolution (JP24ama221540 and JP25ama221540 to HK), and the Platform Project for Supporting Drug Discovery and Life Science Research (JP24ama121034 and JP25ama121034 to HK) from the Japan Agency for Medical Research and Development (AMED), Japan.

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  1. These authors contributed equally: Morihiro Shibasaki, Hiroaki Ikeda

Authors and Affiliations

  1. Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

    Morihiro Shibasaki, Hiroaki Ikeda, Ami Mimura, Taiki Suo, Takefumi Kuranaga & Hideaki Kakeya

  2. Japan Biological Informatics Consortium, Koto-ku, Tokyo, Japan

    Junko Hashimoto

  3. Department of Life Science and Biotechnology, National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo, Japan

    Kazuo Shin-ya

  4. Department of Neurology, Division of Development of Autophagy Modulating Drugs, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan

    Masaya Imoto

Authors
  1. Morihiro Shibasaki
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  2. Hiroaki Ikeda
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  3. Ami Mimura
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  4. Junko Hashimoto
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  5. Taiki Suo
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  6. Takefumi Kuranaga
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  7. Kazuo Shin-ya
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  8. Masaya Imoto
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  9. Hideaki Kakeya
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Correspondence to Hideaki Kakeya.

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Shibasaki, M., Ikeda, H., Mimura, A. et al. Isolation and structure determination of streptospherins B–F, novel cancer stem cell inhibitors, produced by Streptomyces sp. KUSC-240. J Antibiot 78, 535–541 (2025). https://doi.org/10.1038/s41429-025-00843-6

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