Discovery of Zoanthamine Alkaloids from Zoanthus vietnamensis with Antioxidant and Neuroprotective Activities

Two novel alkaloids, zoanides A and B (1 and 2), 12 new zoanthamine-type alkaloids (3-14), together with two known compounds (15 and 16) were obtained from the zoantharian Zoanthus vietnamensis. Their structures and absolute configurations were established by extensive spectroscopic data, DP4+ probability calculation, and X-ray crystallographic analyses. Structurally, compound 1 represents an unusual functionalized skeleton caused by oxidative cleavage; compound 2 possesses an unprecedented 6/6/5/6/7-fused pentacyclic carbon skeleton. Additionally, the plausible biosynthetic pathways of 1 and 2 were proposed. All isolates were evaluated in vitro for neuroprotection. Among them, compounds 2, 3, 8, 9, and 15 exhibited neuroprotection against paclitaxel-induced neurite damage without interfering with the anticancer effects of paclitaxel. Moreover, compounds 2 and 9 demonstrated moderate protective effects against oxaliplatin-induced oxidative stress overload without interfering with the anticancer effects of oxaliplatin.