Marie-Lise Bourguet-Kondracki

Novel alkaloids of the aaptamine class from an Indonesian marine sponge of the genus Xestospongia

Abstract Four novel alkaloids of the aaptamine class have been isolated in addition to the known aaptamine, isoaaptamine, demethyl(oxy)aaptamine and its dimethylketal from an unidentified species of Indonesian marine sponge of the genus Xestospongia . Their structures were elucidated on the basis of detailed 1D and 2D NMR spectroscopic data. Their antimicrobial activity was tested towards Gram (+) ( S. aureus ), Gram (−) ( E. coli , V. anguillarum ) bacterial strains, a fungus ( C. tropicalis ); their cytotoxic activity was evaluated against KB cells.

Bioactive bromopolyacetylenes from the marine sponge Xestospongia testudinaria

Xestospongic acid 1a and its ethyl ester 2, bioactive bromopolyacetylenes, have been isolated from the marine sponge Xestospongia testudinaria. Their structures have been assigned by spectoral methods. Both are antimicrobial and compound 2 is a Na+/K+ ATPase inhibitor.

Cellular Localization of Clathridimine, an Antimicrobial 2-Aminoimidazole Alkaloid Produced by the Mediterranean Calcareous Sponge Clathrina clathrus

Chemical investigation of the Mediterranean calcareous sponge Clathrina clathrus led to the isolation of large amounts of a new 2-aminoimidazole alkaloid, named clathridimine (1), along with the known clathridine (2) and its zinc complex (3). The structure of the new metabolite was assigned by detailed spectroscopic analysis. Clathridimine (1) displayed selective anti-Escherichia coli and anti-Candida albicans activities. Clathridine (2) showed only anti-Candida albicans activity, and its zinc complex (3) exhibited selective anti-Staphylococcus aureus activity. The isolation of analogues of 2-amino-imidazole derivatives from several Leucetta species from various sites in the Pacific Ocean and the Red Sea raises the question of their biosynthetic origin. Microscopic studies revealed abundant extracellular bacteria located in the mesohyl of the sponge, with two predominant morphotypes including spiral bacteria and long, narrow bacilli. Chemical analysis with HPLC/UV/ELSD profiles of sponge cells separated from bacteria by differential centrifugation and trypsinization of the sponge cell surface revealed that clathridine (2) was localized in the sponge cells.

A new β-carboline alkaloid isolated from the marine sponge Hyrtios erecta

A novel β-carboline alkaloid, called hyrtiomanzamine, was isolated from the marine sponge Hyrtios erecta collected in the Red Sea. Its structure elucidation was carried out by application of various one and two D NMR methods. Hyrtiomanzamine 1 is the first 6-OH-β-carboline ring associated to a betaine unit isolated from the marine sponge Hyrtios erecta. Hyrtiomanzamine 1 showed immunosuppressive activity in the B lymphocytes reaction assay.

New bioactive halenaquinone derivatives from South Pacific marine sponges of the genus Xestospongia.

Bioassay-directed fractionation of South Pacific marine sponges of the genus Xestospongia has led to the isolation of a number of halenaquinone-type polyketides, including two new derivatives named xestosaprol C methylacetal 7 and orhalquinone 8. Chemical characterization of these two new compounds was achieved by extensive 1D and 2D NMR spectroscopic studies. Evaluation of anti-phospholipase A(2), anti-farnesyltransferase and antiplasmodial activities of this series is presented and structure/activity relationships are discussed. Orhalquinone 8 displayed a significant inhibition of both human and yeast farnesyltransferase enzymes, with IC(50) value of 0.40 microM and was a moderate growth inhibitor of Plasmodium falciparum.

Identification of Harman as the Antibiotic Compound Produced by a Tunicate-Associated Bacterium

The alkaloid harman, previously reported from some marine invertebrates, was identified as the antibiotic substance of the tunicate-associated bacterium Enterococcus faecium. It exhibited antibacterial activity (MIC, 0.017 mM) against the ichthyopathogenic strain Vibrio anguillarum.

Assessing calcareous sponges and their associated bacteria for the discovery of new bioactive natural products

An overview of the chemistry and microbiology of calcareous sponges (Calcispongiae) is provided, highlighting the potential of these sessile filter-feeding marine invertebrates and their associated bacteria for the discovery of new bioactive natural products. 103 compounds are presented and 116 references cited.

STAT5B-mediated Growth Hormone Signaling Is Organized by Highly Dynamic Microtubules in Hepatic Cells

In the last decade, the notion that microtubules are critical to the spatial organization of signal transduction and contribute to the transmission of signals to downstream targets has been proposed. Because the STAT5B transduction and transcription factor is the major STAT protein activated by growth hormone stimulation in hepatocytes and is a crossroads between many signaling pathways, we studied the involvement of microtubules in STAT5B-mediated growth hormone signaling pathway in the highly differentiated and polarized WIF-B hepatic cell line. We showed that depolymerization of the microtubule network impaired STAT5B translocation to the nucleus upon growth hormone treatment. A significant amount of STAT5B binds to microtubules, while STAT5A and STAT3 are exclusively compartmentalized in the cytosol. Moreover, taxol-induced stabilization of microtubules released STAT5B from its binding, and we show that STAT5B binds specifically to the highly dynamic microtubules and is absent of the stable microtubule subpopulation. The specific involvement of dynamic microtubule subpopulation in growth hormone signaling pathway was confirmed by the inhibition of growth hormone-induced STAT5B nuclear translocation after stabilization of microtubules or specific disruption of highly dynamic microtubules. Upon growth hormone treatment, MT-bound STAT5B was rapidly released from microtubules by a dynein-dependent transport to the nucleus. Altogether, our findings indicate that the labile microtubule subpopulation specifically and dynamically organizes STAT5B-mediated growth hormone signaling in hepatic cells.

DIPUUPEHEDIONE, A CYTOTOXIC NEW RED DIMER FROM A NEW CALEDONIAN MARINE SPONGE HYRTIOS SP.

Dipuupehedione, a cytotox.ic new red diacr 3f pmpehenone was isolated from a New Caledonian marine sponge Hyrtios sp. and its structure established through spectral studies, incjuding extensive 2 D NMR specmscopy. Dipuupehedione is active on KB cells (IC 50 = 3 pg/ml). Copyright Q 1996 Published by Elsevier Science Ltd Our interest in the chemistry of marbe sponges of the genus Hyrtios is due to the variety of compounds1 isolated, many of which with remarkable bioactivity. Typical members are the scalarane-type sesterterpenes, represented by the well-known heteroneminz. As part of our chemical investigation of Hyrtios sponges from New Caledonia, we have previously described 12-epi-heteronemin3 as the major compound from Hyrrios erecta (Keller 1889) a new member of this class of sesterterpenes. We also reported the isolation of sesterterpenes of the manoalide family: thorectolide monoacetate and thorectolide, major products4 of a New Caledonian Hyrtios sp. However, from another marine sponge Hyrrios erecta (Keller 1889) collected in the Red Sea, we have isolated a new and unexpected P-carboline5. We now have studied the metabolites of another New Caledonian Hyrtios specimen. Interestingly, we isolated the known puupehenone, co-OcCuring with a red dimer, the subject of this report. Lyophilized sponges of Hyrrios sp. (500 g), collected by SCUBA diving in New Caledonia (East Coast), were immersed in CH2C12 at room temperature during two days. The crude CH2C12 extract of this sponge showed significant cytotoxic activity on KB cells, antimicrobial activity against Sraphylococcus aurea, antifungal activity against Candida albicans. The CH2C12 extract (7.7 g) was chromatographed on a silica gel column, eluted with hexane/AcOEt 8:2, followed by a Sephadex LH-20 gel fileation (CHCI

Bioactive Indole Derivatives from the South Pacific Marine Sponges Rhopaloeides odorabile and Hyrtios sp.

h4eOH 28) and yielded puupehenone 1 (0.02% dry weight) and compound 2 (0.006% dry weight). Puupehenone was readily identified by comparison with the spectral data reported in the literature6. Compound 2 was obtained as a red glassy solid. In :he Fb.B spectrum the strongest ion was the peak at mlz 653. Preliminary comparison of the spectral data of 1 and 2 showed many similarities. In the IN NMR spectrum, signals in the aliphatic region were almost identical with those of puupehenone 1. The main differences were the lack of two ethylenic protons and the presence of one singlet deshielded proton at 6 4.32 ppm (see Table 1). The 13C NMR spectrum displayed 21 signals, suggesting that 2 should be a symmetrical dimer from 1. High Resolution FAB mass spectrum gave for the ion at m/z 653 the formula C42H5306 (MN+ 653.3842150, A mu +3.7). Moreover, the IR spectrum revealed the absence of an OH group in 2. Absorption maxima in the IR 3861