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

• Published in: Journal of antibiotics 2018-02, Vol.71 (2), p.273-278
• Main Authors: Nakamura, Fumiaki, Kudo, Norio, Tomachi, Yuki, Nakata, Akiko, Takemoto, Misao, Ito, Akihiro, Tabei, Hodaka, Arai, Daisuke, de Voogd, Nicole, Yoshida, Minoru, Nakao, Yoichi, Fusetani, Nobuhiro
• Format: Article
• Language: English
• Subjects: 631/154/309/556; 631/535/1266; 631/92/349; 82/16; 82/58; Animals; Antibiotics; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Bacteriology; Biochemistry; Biomedical and Life Sciences; Bioorganic Chemistry; Crystallography; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Halichondria; HeLa Cells; Humans; Life Sciences; Magnetic Resonance Spectroscopy; Medicinal Chemistry; Microbiology; Models, Molecular; Molecular Structure; Organic Chemistry; original-article; Porifera - chemistry; SIRT1 protein; Sirtuin 1 - antagonists & inhibitors; Sirtuin 2 - antagonists & inhibitors; Sirtuin 3 - antagonists & inhibitors; Sirtuins - antagonists & inhibitors; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet; Steroids; Sterols - isolation & purification; Sterols - pharmacology; Sulfates; X-ray crystallography
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/ja.2017.145

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 IC 50 ranges of 45.9–67.9, 18.9–21.1 and 21.8-37.5 μ M , 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.