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Marine sponges continue to be a rich source of secondary metabolites with novel structures and desirable biological activity. 1 In a continuing search for new protein phosphatase inhibitors from marine organisms, we have isolated a novel cdc25A inhibitor from the marine sponge Dysidea etheria de Laubenfels. The inhibitor, trivially named dysidiolide, is a sesterterpene γ-hydroxybutenolide, and the structure, which represents an unusual cyclization of a C25 isoprenoid, was determined by single-crystal X-ray diffraction. The cdc25 protein phosphatase has been shown to activate the G2/M transition of the cell cycle by the dephosphorylation of the p34cdc2/cyclin B complex at both the Tyr-15 and Thr-14 residues. 2 Cdc25 exists as three human homologs termed cdc25A,-B and-C, the precise functions of which have yet to be fully described. The cdc25A homolog has been cloned and expressed as a GST conjugate in …