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

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 mu 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.