Characterization of metabolites from three tropical Pacific marine invertebrates

Marine organisms produce a wide variety of metabolites that display diverse biological activities and represent an astonishing variety of molecular structural classes. As part of the Ireland group's continuing program to discover novel biologically active marine natural product, three sessile invertebrates from the Fijian and Philippine archipelagos were investigated. Isolation of the compounds described was directed to a large degree by the biological activities displayed by extracts and partitions of the organisms and was accomplished by using standard chromatographic techniques. The structures were solved using standard spectroscopic methods, including one-dimensional (1-D) and two-dimensional (2-D) nuclear magnetic resonance (NMR), infrared (IR) and ultraviolet (UV) spectroscopy, circular dischroism (CD), and low resolution and high resolution fast atom bombardment mass spectrometry (FABMS, HRFABMS). Mamanuthaquinone, a new member of class of quinine containing sesquiterpenoid compounds, was the major metabolite of the Fijian sponge Fasciospongia sp. Mamanuthaquinone is a potent cytotoxic agent with moderate antimicrobial activity. Chemical rearrangement was utilized to determine the absolute stereochemistry of mamanuthaquinone. An unidentifiable orange Fijian sponge of mixed taxonomy, having organizational and chemical characteristics of Axinellidae and Jaspidae families, yielded a new tetracyclic bromophyrrole derivative called epipolasidamide. Epipolasidamide exhibited in vitro cytotoxicity vs. HCT-116 cells, with IC50 of 0.1 mg/mL. Mild cytotoxicity exhibited by the crude extract of Philippino tunicate Eusynstyela misakiensis led to the isolation of eusynstyelamide, a novel dimer of a highly modified 6-bromotryptophan and decarboxylated arginine containing dipeptide. Eusynstyelamide was found to be mildly cytotoxic, with an IC50 of 50 mug/mL vs HCT-116 cells in vitro. The structure was determined by interpretation of 2-D NMR data, including HMBC and COSY45 data. A putative biosynthetic pathway for eusynstyelamide was developed, based on chemotaxonomic and structural evidence.