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At least 235 records · Page 13Linked to original sources

PubMed2002

Antibacterial activity against resistant bacteria and cytotoxicity of four alkaloid toxins isolated from the marine sponge Arenosclera brasiliensis.

Arenosclerins A-C and haliclonacyclamine E, new tetracyclic alkylpiperidine alkaloids isolated from the marine sponge Arenosclera brasiliensis, were subjected to antimicrobial and cytotoxic bioassays. Fourteen samples of microorganisms were used: Candida albicans, Staphylococcus aureus, Escherichia coli, and 12 antibiotic-resistant bacteria isolated from hospital environment. The minimum inhibitory concentration activity of each alkaloid was determined. The four compounds displayed antibacterial activity, but no antifungal activity against C. albicans. Haliclonacyclamine E and arenosclerins A and C were active against a larger number of bacteria strains than arenosclerin B. However, arenosclerins B and C presented more potent antibacterial activity. The alkaloids displayed inhibitory activity against both Gram positive and Gram negative bacteria. Cytotoxicity bioassays using the MTT method showed that these compounds present cytotoxic activity against human HL-60 (leukemia), L929 (fibrosarcoma), B16 (melanoma) and U138 (colon) cancer cell lines at concentrations between 1.5 and 7.0microg/ml. The results obtained indicated that A. brasiliensis alkaloids have a potent toxic activity. The broad cytotoxic and antimicrobial activities presented by A. brasiliensis alkaloids suggest a defensive role of arenosclerins and haliclonacyclamine E against microbial infection and/or the action of potential predators at the sponge's natural habitat.

Alkaloids↗

PubMed2002

Washing out of lipophilic compounds induces a transient increase in the passive Ca(2+) leak in permeabilized A7r5 cells.

We have investigated how the immunosuppressant drug FK506 affected the basal Ca(2+) leak in permeabilized A7r5 cells. Non-mitochondrial Ca(2+) stores loaded to steady state with Ca(2+) slowly lost their accumulated Ca(2+) during incubation in a Ca(2+)-free efflux medium. FK506 up to 100 microM had no effect on the basal Ca(2+) leak. In contrast, the rate of Ca(2+) release proceeded much faster immediately after washing out FK506. The increase in rate of Ca(2+) release after washing out of this compound depended on both its initial concentration and on the time of pre-incubation. A similar effect was also observed after removing another immunosuppressant drug (rapamycin) and after removing the inositol 1,4,5-trisphosphate receptor inhibitor xestospongin C. Since all these substances have a high octanol/H(2)O partition coefficient and accumulate in the endoplasmic reticulum membrane, we suggest that the transient increase in the basal Ca(2+) leak is due to the sudden removal of these lipophilic substances from the membrane.

Animals↗

PubMed2002

(+)-7S-Hydroxyxestospongin A from the marine sponge Xestospongia sp. and absolute configuration of (+)-xestospongin D.

The structure of the title compound, (+)-7S-hydroxyxestospongin A was solved by single-crystal X-ray diffraction analysis and the absolute stereochemistry obtained by analysis of the derived R and S Mosher's esters. The absolute configuration of xestospongin D was determined for the first time by analysis of anomalous scattering from the X-ray crystal diffraction data set. Xestospongins A, C, and D, araguspongine C, and demethylxestospongin B exhibited modest antifungal activity (MIC 30-100 g/mL) against various fluconazole-resistant Candida spp., but 7S-hydroxyxestospongin A was inactive.

Alkaloids↗

PubMed2006

X-ray diffraction and theoretical studies for the quantitative assessment of intermolecular arene-perfluoroarene stacking interactions.

The arene-perfluoroarene stacking interaction was studied by experimental and theoretical methods. A series of compounds with different possibilities for formation of this recognition motif in the solid state were synthesized, and their crystal structures determined by single-crystal X-ray diffraction. The crystal packing of these compounds, as well as the packing of related compounds retrieved from crystallographic databases, were analyzed with quantitative crystal potentials: total lattice energies and the cohesive energies of closest molecular pairs in the crystals were calculated. The arene-perfluoroarene recognition motif emerges as a dominant interaction in the non-hydrogen-bonding compounds studied here, to the point that asymmetric dimers formed over the stacking motif carry over to asymmetric units made of two molecules in the crystal both for pure compounds and for molecular complexes; however, inter-ring distances and angles range from 3.70 to 4.85 A and from 5 to 21 degrees , respectively. Pixel energy partitioning reveals that whenever aromatic rings stack, the largest cohesive energy contribution comes from dispersion, which roughly amounts to 20 kJ mol(-1) per phenyl ring, while the coulombic term is minor but significant enough to make a difference between the arene-arene or perfluoroarene-perfluoroarene interactions on the one hand, and arene-perfluoroarene interactions on the other, whereby the latter are favored by about 10 kJ mol(-1) per phenyl ring. No evidence of special interaction which can be attributed to HF confrontation was recognizable.

Crystallography, X-Ray↗

PubMed2006

Antiviral interactions of an HCV polymerase inhibitor with an HCV protease inhibitor or interferon in vitro.

The combinations of Abbott Hepatitis C virus (HCV) polymerase A-782759 with either Boehringer Ingelheim HCV NS3 protease inhibitor BILN-2061 or interferon (IFN) displayed additive to synergistic relationships over a range of concentrations of two-drug combination. Treatment of HCV replicon with A-782759, IFN or BILN-2061 for about 16 days resulted in dramatic reductions in HCV RNA (5.1, 3.0 and 3.9 log10 RNA copies, respectively). However, none of the compounds tested alone lead to replicon RNA reduction to undetectable levels. Ongoing replication in the presence of A-782759 or BILN-2061 was associated with the appearance of resistant mutations M414T in NS5B and D168V in NS3, respectively. In contrast, a combination of A-782759 with BILN-2061 resulted in greater than 7 logs RNA reduction leading to undetectable replicon RNA after 16 days of treatment. Our findings suggest that a monotherapy with either drug alone is likely to result in development of resistant mutants. However, a combination therapy with polymerase inhibitor has the potential to improve the efficacy of IFN or a protease inhibitor alone in vivo, due to the lower likelihood of resistance development.

Antiviral Agents↗

PubMed2002

Inhibitory mechanism of xestospongin-C on contraction and ion channels in the intestinal smooth muscle.

1. Xestospongin-C isolated from a marine sponge, Xestospongia sp., has recently been shown to be a membrane-permeable IP(3) receptor inhibitor. In this study we examined the effects of this compound on smooth muscle from guinea-pig ileum. 2. In guinea-pig ileum permeabilized with alpha-toxin, xestospongin-C (3 microM) inhibited contractions induced by Ca(2+) mobilized from sarcoplasmic reticulum (SR) with IP(3) or carbachol with GTP, but not with caffeine. 3. In intact smooth muscle tissue, xestospongin-C (3-10 microM) inhibited carbachol- and high-K+-induced increases in [Ca(2+)](i) and contractions at sustained phase. 4. It also inhibited voltage-dependent inward Ba(2+) currents in a concentration-dependent manner with an IC(50) of 0.63 microM. Xestospongin-C (3-10 microM) had no effect on carbachol-induced inward Ca(2+) currents via non-selective cation channels; but it did reduce voltage-dependent K+ currents in a concentration-dependent manner with an IC(50) of 0.13 microM. 5. These results suggest that xestospongin-C inhibits the IP(3) receptor but not the ryanodine receptor in smooth muscle SR membrane. In intact smooth muscle cells, however, xestospongin-C appears to inhibit voltage-dependent Ca(2+) and K+ currents at a concentration range similar to that at which it inhibits the IP(3) receptor. Xestospongin-C is a selective blocker of the IP(3) receptor in permeabilised cells but not in cells with intact plasma membrane.

Animals↗

PubMed2004