Dentithecamides A–H, Diacylated Zoanthoxanthin Derivatives with PAX3-FOXO1 Inhibitory Activity from the Hydroid Dentitheca habereri

Chemical investigation of the marine hydroid Dentitheca habereri led to the identification of eight new diacylated zoanthoxanthin alkaloids, named dentithecamides A–H (1–8), along with three previously reported analogues, zoamides B–D (9–11). The structures of compounds 1–11 were elucidated by spectroscopic and spectrometric analyses, including IR, HRESIMS, and NMR experiments, and by comparison with literature data. Compounds 1–11 are the first zoanthoxanthin alkaloids to be reported from a hydroid. Dentithecamides A (1) and B (2) along with zoamides B–D (9–11), which all share a conformationally mobile cycloheptadiene core, inhibited PAX3-FOXO1 regulated transcriptional activity and thus provided a structural framework for the potential development of more potent PAX3-FOXO1 inhibitors.