Cembrane-type diterpenoids from the South China Sea soft coral Sarcophyton mililatensis

Abstract

Eight cembrane-type diterpenoids, namely, (+)-(6<i>R</i>)-6-hydroxyisosarcophytoxide (<b>1</b>), (+)-(6<i>R</i>)-6-acetoxyisosarcophytoxide (<b>2</b>), (+)-17-hydroxyisosarcophytoxide (<b>3</b>), sarcomililatins A-D (<b>4</b>-<b>7</b>), and sarcomililatol (<b>8</b>), were isolated from the soft coral <i>Sarcophyton mililatensis</i> collected from Weizhou Island, Guangxi Autonomous Region, together with 2 known related analogues, (+)-isosarcophytoxide (<b>9</b>) and (+)-isosarcophine (<b>10</b>). The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. The absolute configuration of compound <b>1</b> was established by the modified Mosher׳s method, while the absolute configurations of compounds <b>4</b> and <b>5</b> were assigned by electronic circular dichroism (ECD) spectroscopy and that of compound <b>8</b> was established by time-dependent density functional theory electronic circular dichroism (TD-DFT ECD) calculation. In <i>in vitro</i> bioassays, compound <b>9</b> displayed significant cytotoxicity against the human cancer cell lines human promyelocytic leukemia cells (HL-60) and human lung adenocarcinoma cells (A-549) with IC₅₀ values of 0.78±0.21 and 1.26±0.80 μmol/L, respectively. Compounds <b>4</b> and <b>9</b> also showed moderate inhibitory effects on the TNF<i>α</i>-induced Nuclear factor kappa B (NF-<i>κ</i>B, a therapeutical target in cancer) activation, showing IC₅₀ values of 35.23±12.42 and 22.52±4.44 μmol/L, respectively.