New Steroids with a Rearranged Skeleton as (h)P300 Inhibitors from the Sponge Theonella swinhoei

Swinhoeisterols A (1) and B (2), two novel sterols with an unprecedented 6/6/5/7 ring system, were isolated from the sponge Theonella swinhoei. The structures and absolute configurations were elucidated by spectroscopic analysis, X-ray single-crystal diffraction, modified Mosher's method, and TDDFT/ECD calculations. The cytotoxicity of these compounds toward A549 and MG-63 cells encourages studies on their potential target using an inverse virtual screening approach. The predicted inhibitor of h(p300) was corroborated by an in vitro biological test.

斯氏海绵甾醇A（1）和B（2）是两种具有前所未有的6/6/5/7环系的新型甾醇，从海绵Theonella swinhoei中分离得到。通过光谱分析、X射线单晶衍射、改进的Mosher法以及含时密度泛函理论/电子圆二色谱计算阐明了其结构和绝对构型。这些化合物对A549和MG - 63细胞的细胞毒性促使利用反向虚拟筛选方法对其潜在靶点进行研究。通过体外生物学试验证实了其对人（p300）的预测抑制作用。