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 1–3 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).
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Nakamura, F., Kudo, N., Tomachi, Y. et al. Halistanol sulfates I and J, new SIRT1–3 inhibitory steroid sulfates from a marine sponge of the genus Halichondria. J Antibiot 71, 273–278 (2018). https://doi.org/10.1038/ja.2017.145
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DOI: https://doi.org/10.1038/ja.2017.145
