Anti-Lymphangiogenesis Components from Zoanthid Palythoa tuberculosa

Abstract

Three new compounds, tuberazines A–C (1–3), and eleven known compounds (4–14) were obtained from the ethanolic extract of Taiwanese zoanthid Palythoa tuberculosa. Compounds 1–4 are rare marine natural products with a pyrazine moiety, and compound 5 is a tricyclic tryptamine derivative isolated from nature for the first time. The structures of all isolated metabolites were determined by analyzing their IR, Mass, NMR, and UV spectrometric data. The absolute configuration of 1 was confirmed by comparing the trend of experimental electronic circular dichroism (ECD) with calculated ECD spectra. The anti-lymphangiogenic activities of new compounds were evaluated in human lymphatic endothelial cells (LECs). Of these, new compound 3 displayed the most potent anti-lymphangiogenesis property by suppressing cell growth and tube formation of LECs.

Phomaketide A Inhibits Lymphangiogenesis in Human Lymphatic Endothelial Cells

“…HL-85-ALS5-R004, has been reported to suppress lymphangiogenesis by down-regulating the VEGF-C/VEGFR-3 cascade [26]. A recent study has shown that tuberazines C obtained from Taiwanese zoanthid Palythoa tuberculosa displayed the anti-lymphangiogenesis effect through the suppression of cell growth and tube formation in human LECs [14]. Here, we discover that phomaketide A, isolated from the marine endophytic fungal strain Phoma sp.…”

“…Figure 1B illustrates how phomaketide A inhibited LECs growth in a concentration-dependent manner (IC 50 = 3.7 ± 0.6 μM). The lymphangiogenesis inhibitor, rapamycin, served as a positive control [14]. Next, the results of a tube formation assay showed that phomaketide A significantly reduced LECs tube formation (Figure 2A).…”

“…A549-Leu cells were maintained in DMEM, supplemented with 10% fetal bovine serum (FBS). The cells culture conditions are recorded in our previous paper [14].…”

“…Overnight, the culture medium was replaced with fresh EGM-2MV medium in the presence of either vehicle (DMSO) or phomaketide A for 48 h treatment. The assay on cell growth of LECs was determined by the method based on our previous study [14].…”

“…LECs were seeded at a density of 2 × 10 4 cells per well and incubated in EGM-2MV medium and the indicated concentration of tested compounds, for 8 h at 37 °C. The detection and quantification of LECs tube formation were examined according to previously described procedures [14].…”