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

Fumiaki Nakamura; Norio Kudo; Yuki Tomachi; Akiko Nakata; Misao Takemoto; Akihiro Ito; Hodaka Tabei; Daisuke Arai; Nicole de Voogd; Minoru Yoshida; Yoichi Nakao; Nobuhiro Fusetani

doi:10.1038/ja.2017.145

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

J Antibiot (Tokyo). 2018 Feb;71(2):273-278. doi: 10.1038/ja.2017.145. Epub 2017 Nov 29.

Authors

Fumiaki Nakamura¹, Norio Kudo², Yuki Tomachi¹, Akiko Nakata², Misao Takemoto², Akihiro Ito^{3

4}, Hodaka Tabei¹, Daisuke Arai⁵, Nicole de Voogd⁶, Minoru Yoshida^{2

3

7}, Yoichi Nakao^{1

5}, Nobuhiro Fusetani^{5

8}

Affiliations

¹ Department of Chemistry and Biochemistry, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
² Seed Compounds Exploratory Unit for Drug Discovery Platform, RIKEN Center for Sustainable Resource Science, Saitama, Japan.
³ Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Saitama, Japan.
⁴ School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
⁵ Research Institute for Science and Engineering, Waseda University, Tokyo, Japan.
⁶ Naturalis Biodiversity Center, Leiden, The Netherlands.
⁷ Department of Biotechnology, Graduate School of Agricultural Life Sciences, The University of Tokyo, Tokyo, Japan.
⁸ Fisheries and Oceans Hakodate, Hakodate, Japan.

PMID: 29184120
DOI: 10.1038/ja.2017.145

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.

MeSH terms

Animals
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / pharmacology
Crystallography, X-Ray
Drug Screening Assays, Antitumor
HeLa Cells
Humans
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Structure
Porifera / chemistry*
Sirtuin 1 / antagonists & inhibitors
Sirtuin 2 / antagonists & inhibitors
Sirtuin 3 / antagonists & inhibitors
Sirtuins / antagonists & inhibitors*
Spectrometry, Mass, Electrospray Ionization
Spectrophotometry, Ultraviolet
Sterols / isolation & purification*
Sterols / pharmacology*

Substances

Antineoplastic Agents
Sterols
halistanol trisulfate
SIRT1 protein, human
SIRT2 protein, human
SIRT3 protein, human
Sirtuin 1
Sirtuin 2
Sirtuin 3
Sirtuins