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Isolation and structures of erylosides from the carribean sponge Erylus formosus

Nine new triterpene glycosides, erylosides F1-F4 (1-4), M (5), N (6), O (7), P (8), and Q (9), along with previously known erylosides F (10) and H (11) were isolated from the sponge Erylus formosus collected from the Mexican Gulf (Puerto Morelos, Mexico). Structures of 1-4 were determined as the corresponding biosides having aglycons related to penasterol with additional oxidation patterns in their side chains. Erylosides 5-9 contain new variants of carbohydrate chains with three (5, 6), four (7), and six (8, 9) sugar units, respectively. Erylosides 5, 7, 8, and 6, 9 contain 14-carboxy-24-methylenelanost-8(9)-en-3beta-ol and penasterol as aglycons, respectively. In contrast with its epimer 2, the compound 3 induced the early apoptosis of Ehrlich carcinoma cells at a concentration of 100 mug/mL, while 1 and 10 activated the Ca2+ influx into mouse spleenocytes (130% of the control) at the same doses.

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Tetrahydropyran – Wikipedia,
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Delivery of cholesteryl-conjugated phosphorothioate oligodeoxynucleotides to Kupffer cells by lactosylated low-density lipoprotein

The efficacy of antisense oligonucleotides depends on the ability to reach in vivo their target cells. We aim to develop strategies to enhance uptake of phosphorothioate oligodeoxynucleotides by Kupffer cells. To this end, we conjugated cholesterol to ISIS-3082, a phosphorothioate oligodeoxynucleotide specific for intercellular adhesion molecule-1. The cholesterol-conjugated oligonucleotide, denoted ISIS-9388, associated readily with lactosylated low-density lipoprotein (LacLDL), a lipidic carrier that is taken up by galactose receptors on Kupffer cells. Association of up to 10 molecules of ISIS-9388 per LacLDL particle did not induce aggregation. LacLDL-associated [3H]ISIS-9388 was rapidly taken up by the liver after injection into rats (52.9 ± 1.8% of the dose within 2 min versus 18.6 ± 2.8% for ISIS-3082). N-acetylgalactosamine inhibited hepatic uptake, indicating involvement of galactose-specific receptors. Liver cells were isolated at 60 min after injection of LacLDL-associated [3H]ISIS-9388. Kupffer cells displayed the highest uptake: 88.1 ± 24.7 ng of oligonucleotide/mg of cell protein, which is 6-14 times higher than after injection of free ISIS-9388 or ISIS-3082 (15.0 ± 3.8 ng and 6.3 ± 1.4 ng, respectively). It can be calculated that Kupffer cells contribute 43.9 ± 5.4% to the liver uptake (free ISIS-9388 and ISIS-3083 14.5 ± 3.1% and 8.3 ± 3.2%, respectively). In conclusion, conjugation of a phosphorothioate oligodeoxynucleotide with cholesterol and its subsequent association with LacLDL results in a substantially increased Kupffer cell uptake of the oligonucleotide. As Kupffer cells play a key role in inflammation, our approach may be utilized to improve antisense-based therapeutic intervention during inflammation.

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PROTEIN KINASE INHIBITORS

The present invention relates to a novel family of inhibitors of protein kinases. In particular, the present invention relates to inhibitors o f the members o f the Tec and Src protein kinase families

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Glucosamine and Glucosamine/Anti-Inflammatory Mutual Prodrugs, Compositions, and Methods

Mutual prodrugs of glucosamine, and derivatives and analogs of glucosamine and an anti-inflammatory agent, compositions thereof, and methods for, e.g., treating disorders and conditions by administration of the compositions are provided. Topical compositions of glucosamine, and derivatives and analogs of glucosamine are also provided.

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Regioselective aromatic monobromination of alkyl phenyl ethers with NaClO2, NaBr, Mn(acac)3, and Montmorillonite K10 in dichloromethane

Regioselective and high-yielding nuclear monobromination of aromatic ethers can be accomplished with a combination of NaClO2, NaBr, and Mn(acac)3 catalyst in dilchloromethane under mild and neutral conditions with the aid of Montmorillonite K10.

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17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analogues

17(R),18(S)-Epoxyeicosatetraenoic acid [17(R),18(S)-EETeTr], a cytochrome P450 epoxygenase metabolite of eicosapentaenoic acid (EPA), exerts negative chronotropic effects and protects neonatal rat cardiomyocytes against Ca 2+-overload with EC50 ? 1-2 nM. Structure-activity studies revealed that a cis-Delta11,12- or Delta14,15- olefin and a 17(R),18(S)-epoxide are minimal structural elements for antiarrhythmic activity whereas antagonist activity was often associated with the combination of a Delta14,15-olefin and a 17(S),18(R)-epoxide. Compared with natural material, the agonist and antagonist analogues are chemically and metabolically more robust and several show promise as templates for future development of clinical candidates.

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Enzymatic galactosylation of cello- and chito-oligomers

Terminal galactosylations of cello- and chito-oligomers are studied employing galactosyltransferase with and without alpha-lactalbumin. The lactose synthase complex allows just for galactosylation of cellobiose in lower yield but not for higher cello-oligomers. In contrast, the affinity in galactosylation of chito-oligomers increases with higher members to reach the maximum at chitohexaose with only a 30% reduction in transfer rate. In addition to kinetic data, preparative studies with a number of acceptor substrates gave galactosylated oligosaccharides in high yields. (Figure Presented). Copyright Taylor & Francis Group, LLC.

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METHODS AND COMPOSITIONS FOR MODIFIED RELEASE OF NUTRITIONAL SUPPLEMENTS

The present invention relates to the modified release of nutritional supplements by combining one or more isolated and purified long-chain polysaccharides and one or more nutritional supplements selected from anti-oxidants, vitamins, minerals, amino acids, nucleic acids, mixtures and combinations thereof, wherein the supplement is compressed at a pressure greater that 100 psi.

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Enantioselective alcoholysis of meso-glutaric anhydrides catalyzed by Cinchona-based sulfonamide catalysts

The bifunctional Cinchona-based sulfonamide catalysts showed the highest levels of enantioselectivity reported to date in the alcoholytic desymmetrization of meioglutaric anhydrides. Density functional theory (DFT) computational studies provide detailed insight into the observed sense of enantioselectivity. Moreover, detailed experimental studies and single crystal X-ray analysis confirmed that these bifunctional organocatalysts 3 do not form Hbonded self-aggregates in both solution and solid state. The synthetic utility of this methodology was also demonstrated in the synthesis of pharmaceutically important gamma-amino acids, such as (S)-pregabalin. Of the many asymmetric syntheses of enantiomerically pure (S)-pregabalin reported to date, our synthesis requires the least number of and the simplest steps.

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Tetrahydropyran – Wikipedia,
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Kinetics and mechanism of degradation of chitosan by combining sonolysis with H2O2/ascorbic acid

This study demonstrated the combined use of sonolysis with the H2O2/ascorbic acid (Vc) redox reaction to degrade chitosan (CS). The influence of operating parameters, such as the initial CS concentration (1-15 mg mL-1), the input power level (15-45% of the total input power), the H2O2 and Vc concentration (10-70 mM) and the pH (3.0-5.0) of the reaction solution, on the molecular weight and degradation kinetics of CS were investigated and optimized. Based on the degradation kinetics, a synergetic effect of sonolysis with H2O2 and Vc on the degradation of CS was observed. Structural analysis by FT-IR and 1H and 13C NMR indicated no significant difference between the chemical structure of chitosan before and after degradation. Moreover, intermolecular hydrogen bonds were broken, and the crystallinity of degraded chitosan decreased. Using the above analysis, CS degradation by the combination of sonolysis with the H2O2/Vc redox reaction was proposed to be due to mechanical effects along with HO attack on the beta-1,4-glucoside linkages of glucosamine units. These results suggest that the sonolysis/H2O2/Vc combined technique is promisingly suitable for large-scale manufacture of chitooligosaccharide.

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