Discovery of Zoanthamine Alkaloids from <i>Zoanthus vietnamensis</i> with Antioxidant and Neuroprotective Activities

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