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Isolation of new derivatives of the 20-membered macrodiolide bispolide from Kitasatospora sp. MG372-hF19

The Journal of Antibiotics volume 75, pages 77–85 (2022)Cite this article

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Abstract

New three macrocyclic diolides, named bispolides C-E (1–3), were isolated from a fermentation broth of the actinomycete strain MG372-hF19, which produces an indole glycoside and leptomycins as we reported previously. The absolute structures of compounds 1–3 were elucidated by NMR and X-ray crystallography. Compounds 1–3 diverge from the known nine bispolides in their different alkylation patterns on the 20-membered macrocyclic diolide skeleton and the side chain in their planar structures. Furthermore, compounds 1–3 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci and cytotoxic activity against human cancer cell lines. Among them, compound 3 has the most potent biological activities against bacteria and tumor cells. Additionally, using a membrane-potential-sensitive fluorescence probe, we found that compounds 1–3 and elaiophylin have a similar effect on membrane potential in A549 human lung cancer cells.

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Acknowledgements

The authors thank Dr. I. Momose and Mr. S. Ohba for technical assistance and discussion. The authors also thank the Molecular Profiling Committee, Grant-in-Aid for Scientific Research on Innovative Areas “Advanced Animal Model Support (AdAMS)” from The Ministry of Education, Culture, Sports, Science and Technology, Japan (JSPS KAKENHI Grant Number JP 16H06276). This work was supported in part by grants from JSPS KAKENHI Grant Number 17K08777.

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Authors and Affiliations

  1. Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Shizuoka, Japan

    Yasuko Kohda, Shuichi Sakamoto & Manabu Kawada

  2. Institute of Microbial Chemistry (BIKAKEN), Laboratory of Microbiology, Microbial Chemistry Research Foundation, Tokyo, Japan

    Maya Umekita, Rie Arisaka, Yuko Shibuya, Hideyuki Muramatsu & Masayuki Igarashi

  3. Institute of Microbial Chemistry (BIKAKEN), Laboratory of Molecular Structure Analysis, Microbial Chemistry Research Foundation, Tokyo, Japan

    Tomoyuki Kimura, Yumiko Kubota & Ryuichi Sawa

  4. Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan

    Shingo Dan

  5. Institute of Microbial Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation, Tokyo, Japan

    Manabu Kawada

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  1. Yasuko Kohda
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Correspondence to Shuichi Sakamoto or Masayuki Igarashi.

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Kohda, Y., Sakamoto, S., Umekita, M. et al. Isolation of new derivatives of the 20-membered macrodiolide bispolide from Kitasatospora sp. MG372-hF19. J Antibiot 75, 77–85 (2022). https://doi.org/10.1038/s41429-021-00492-5

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