Sunday, March 16, 2014

Unique Steroid Structures Recently Isolated from Marine Sponges

            Among the thousands of naturally occurring steroidal derivatives, poly-halogenated ones are particularly rare. However, in 2004, a tetrachlorinated androstane deriviative, clionastatin B, was isolated from the tropical burrowing sponge Cliona nigricans. Clionastatin B represents the first example of a poly-halogenated steroid found in nature, from either a marine or terrestrial source. The clionastatins displayed potent cytotoxicity against three different tumor cell lines, with IC50 values ranging from 0.8 to 2.0 ug/mL. Recently, the laboratory of Vanderwal at the University of California, Irvine completed an elegant synthesis of the A-C tricyclic western substructure of the highly chlorinated androstane clionastatin B which provides strong support for the original 2004 structural assignment.
            Dredging or trawling of the ocean floor for deep-water marine organisms is an effective method to collect fragments of organisms that coexist, hundreds of meters below the ocean’s surface. Deep-water marine organisms often produce rare metabolites that exhibit interesting bioactivities. Recently, the extracts of frozen fragments obtained from dredging expeditions yielded a new steroid, cinanthrenol A. The steroidal framework of cinanthrenol A is comprised of a phenanthrene domain (highlighted above in blue) and an ornate eastern spiro[2,4]heptane system. Until recently, phenanthrene-containing natural products were known only from plants. It was demonstrated by fluorescence and HPLC techniques that cinanthrenol A is produced by the sponge, Cinachyrella sp. The natural product binds to the estrogen receptor in a relative binding assay with an IC50 value of 10 nM, thus indicating that cinanthrenol A has strong estrogenic activity.

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