Latrunculin U: a potent actin-disrupter from the Red Sea marine sponge <i>Negombata magnifica</i>

During our efforts to identify biologically active compounds from Red Sea marine invertebrates, a new compound, latrunculin U (<b>1</b>), was identified from the Red Sea sponge <i>Negombata magnifica</i> along with latrunculins A (<b>2</b>), B (<b>3</b>), and 16-<i>epi</i>-latrunculin B (<b>4</b>). The structures of the latrunculins were elucidated based on a combination of comprehensive 1D and 2D NMR analyses and high-resolution mass spectral determinations. The antiproliferative potency of each compound in HeLa cells was evaluated, and they had IC₅₀ values ranging from 0.31 to 1.64 μM. The antiproliferative activities of the compounds indicated that latrunculins with a 16-membered macrocyclic lactone moiety (<b>1</b> and <b>2</b>) were more potent than those of the 14-membered compounds (<b>3</b> and <b>4</b>), suggesting the importance of the size of the macrolide moiety for optimal activity. All four compounds promoted disruption of the actin cytoskeleton in cells, consistent with the reported actin-disrupting effects of this compound class.