Original Article

Halistanol sulfates I and J, new SIRT1–3 inhibitory steroid sulfates from a marine sponge of the genus Halichondria

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Abstract

Two new analogs of halistanol sulfate (1) were isolated from a marine sponge Halichondria sp. collected at Hachijo-jima Island. Structures of these new halistanol sulfates I (2) and J (3) were elucidated by spectral analyses. Compounds 13 showed inhibitory activity against SIRT 1-3 with IC50 ranges of 45.9–67.9, 18.9–21.1 and 21.8-37.5 μM, respectively. X-ray crystallography of the halistanol sulfate (1) and SIRT3 complex clearly indicates that 1 binds to the exosite of SIRT3 that we have discovered in this study.

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Acknowledgements

This paper is a part of the outcome of research performed under a Waseda University Grant-in-Aid for Scientific Research, the Strategic Research Platforms for Private University, a Matching Fund Subsidy from the Ministry of Education, Science, Sports, and Technology (MEXT), Japan, JSPS KAKENHI Grant Number 26221204 and the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct). This work was inspired by the JSPS Asian Chemical Biology Initiative. This work was performed under the approval of the Photon Factory Program Advisory Committee (Proposal Nos. 2013G674 and 2015G615). Atomic coordinates and structural factors have been deposited in the Protein Data Bank (PDB id 3GLU).

Author information

Author notes

    • Fumiaki Nakamura
    •  & Norio Kudo

    These authors contributed equally to this work.

Affiliations

  1. Department of Chemistry and Biochemistry, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan

    • Fumiaki Nakamura
    • , Yuki Tomachi
    • , Hodaka Tabei
    •  & Yoichi Nakao
  2. Seed Compounds Exploratory Unit for Drug Discovery Platform, RIKEN Center for Sustainable Resource Science, Saitama, Japan

    • Norio Kudo
    • , Akiko Nakata
    • , Misao Takemoto
    •  & Minoru Yoshida
  3. Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Saitama, Japan

    • Akihiro Ito
    •  & Minoru Yoshida
  4. School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

    • Akihiro Ito
  5. Research Institute for Science and Engineering, Waseda University, Tokyo, Japan

    • Daisuke Arai
    • , Yoichi Nakao
    •  & Nobuhiro Fusetani
  6. Naturalis Biodiversity Center, Leiden, The Netherlands

    • Nicole de Voogd
  7. Department of Biotechnology, Graduate School of Agricultural Life Sciences, The University of Tokyo, Tokyo, Japan

    • Minoru Yoshida
  8. Fisheries and Oceans Hakodate, Hakodate, Japan

    • Nobuhiro Fusetani

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Competing interests

The authors declare no conflict of interest.

Corresponding authors

Correspondence to Minoru Yoshida or Yoichi Nakao.

Supplementary information

Supplementary Information accompanies the paper on The Journal of Antibiotics website (http://www.nature.com/ja)