In a new study, 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.

Metastasis is a major cause of death in cancer patients. The metastatic spread of tumor cells to sentinel lymph nodes represents the crucial step of tumor dissemination in many types of human cancer.

Lymphangiogenesis, the formation of new lymphatic vessels from preexisting ones, is essential for the progression of cancer metastasis. Therefore, lymphangiogenesis represents a potential therapeutic target for preventing lymphatic metastasis.

Zoanthids are radially symmetrical cnidarians with two rows of tentacles, and they are usually found on the rocky coast of subtropical and tropical areas. Zoanthids are regarded as rich sources of novel secondary metabolites with diverse bioactivities.

In the bioactive screening of Taiwanese zoanthids, the ethanolic extract of P. tuberculosa was found to have significant anti-cancer and anti-lymphangiogenic activities. Therefore, a series of bioassay-guided fractionations for these animal materials were carried out.

The separation, structural elucidation, and bioactivities of three new and eleven known compounds from P. tuberculosa are herein reported. Three new compounds, tuberazines A-C, and eleven known compounds were obtained from the ethanolic extract of Taiwanese zoanthid Palythoa tuberculosa.

The structures of all isolated metabolites were determined by analyzing their IR, Mass, NMR, and UV spectrometric data. The absolute configuration of compounds was confirmed by comparing the trend of experimental electronic circular dichroism (ECD) with calculated ECD spectra.

Marine natural products with pyrazine ring systems are quite rare. Only a few marine invertebrates were reported to produce pyrazine derivatives such as clavulazine, clavulazols, palythazine, barrenazines, botryllazines, and asteropterin.

Those compounds usually demonstrated diverse pharmacological properties. For example, barrenazines showed potent anti-tumor activity, which resulted in the development of total synthesis.

In the new manuscript, three new dihydropyranopyrazine derivatives were identified and their anti-lymphangiogeneic activity was first unveiled. The study findings not only extend the structural uniqueness of zoanthids, but provide further insight into pyrazine as an anti-lymphangiogeneic agent.