Anti-Lymphangiogenic Alkaloids from the Zoanthid Zoanthus vietnamensis Collected in Taiwan

Eleven new secondary metabolites [kuroshines H–J (1–3), 27-methyl glycinate zoanthenamine (4), 27-hydroxyzoanthenamine (5), 27-methyl glycinate kuroshine A (6), 27-hydroxykuroshine A (7), 3β-hydroxy-28-deoxyzoanthenamine (8), 14α-hydroxy-28-deoxyzoanthenamine (9), 27-hydroxy-28-deoxyzoanthenamine (10), and kuroshine K (11)], along with seven known compounds (12–18), were isolated from the zoantharian Zoanthus vietnamensis. The structures of all isolated components were elucidated by spectroscopic data (IR, MS, NMR, and UV), especially 2D NMR analyses. The relative configurations of 1 and 2 were confirmed by using single-crystal X-ray crystallography. Compounds 1–3 were found to have an unprecedented ether linkage between C-15 and C-28, while the unusual substituent methyl glycinate, attached at C-27 in compounds 4 and 6, was found for the first time in zoanthamine-type alkaloids. The anti-lymphangiogenic activities of 17 isolated compounds were evaluated. Compounds 4, 5, and 10 exerted promising anti-lymphangiogenic functions by reducing cell growth and tube formation of human lymphatic endothelial cells (LECs). In addition, the structure–activity relationships of the isolated alkaloids against lymphangiogenesis of LECs are discussed.