No abstract

Silica gel column chromatography, followed by HPLC purification on the apolar fraction of the methanol extract of marine sponge Theonella swinhoei, resulted in the isolation of a library of 10 polyhydroxylated steroids which we named theonellasterols B-H (1-7) and conicasterols B-D (8-10). The structures were determined on the basis of extensive spectroscopic data (MS, (1)H and (13)C NMR, COSY, HSQC, HMBC, and ROESY) analysis, and the putative binding mode to nuclear receptors (NRs) has been obtained through docking calculations. Pharmacological and structure-activity relationship analysis demonstrate that these natural polyhydroxylated steroids are potent ligands of human nuclear pregnane receptor (PXR) and modulator of farnesoid-X-receptor (FXR). In addition, the molecular characterization of theonellasterol G allowed the identification of the first FXR modulator and PXR ligand so far identified. Exposure of liver cells to this agent resulted in potent induction of PXR-regulated genes and modulation of FXR-regulated genes, highlighting its pharmacological potential in the treatment of liver disorders.

A total of 19 steroids, of which 13 steroidal oligoglycosides (nine new and four known) and six polyhydroxylated steroids (four new and two known), has been isolated from the Antarctic starfish Acodontaster conspicuus. The mixture is dominated by glycosides composed of steroidal aglycons having the hydroxyl groups typically disposed on one side of the tetracyclic nucleus, i.e., 3 beta,4 beta,6 alpha,8,15 beta-, with some having a sulfate at C-6, and differing in the side chains and/or in the disaccharide moieties that are usually attached at C-26, with some at C-28 and C-29. Those compounds are accompanied by minute amounts of glycosides with a delta 8(14)-double bond in the steroid, which is a structural feature not previously found among polyhydroxysteroids derived from starfish. Small amounts of six related unglycosidated polyhydroxysteroids and three higher-molecular-weight asterosaponins complete the composition of the mixture. The structures of the new compounds were determined by interpretation of their spectral data and by comparison with spectral data of known compounds. Eighteen of these compounds were evaluated for their ability to inhibit growth in Antarctic marine bacteria isolated from either the water column or the surfaces of benthic marine invertebrates. Of these compounds, 50% were active against at least one Antarctic marine bacterium. This suggests that these compounds may play an important role in deterring microbial fouling.