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

During our efforts to identify biologically active compounds from Red Sea marine invertebrates, a new compound, latrunculin U (1), was identified from the Red Sea sponge Negombata magnifica along with latrunculins A (2), B (3), and 16-epi-latrunculin B (4). 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 (1 and 2) were more potent than those of the 14-membered compounds (3 and 4), 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.