| 1. |
- Czeiter, Endre, et al.
(författare)
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Calpain inhibition reduces axolemmal leakage in traumatic axonal injury
- 2009
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 14:12, s. 5115-5123
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Tidskriftsartikel (refereegranskat)abstract
- Calcium-induced, calpain-mediated proteolysis (CMSP) has recently been implicated to the pathogenesis of diffuse (traumatic) axonal injury (TAI). Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP) alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA) and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA) was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor) or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI.
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| 2. |
- Isarankura-Na-Ayudhya, Chartchalerm, et al.
(författare)
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Computational Insights on Sulfonamide Imprinted Polymers
- 2008
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Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 13:12, s. 3077-3091
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Tidskriftsartikel (refereegranskat)abstract
- Molecular imprinting is one of the most efficient methods for preparing synthetic receptors that possess user defined recognition properties. Despite general success of non-covalent imprinting for a large variety of templates, some groups of compounds remain difficult to tackle due to their structural complexity. In this study we investigate preparation of molecularly imprinted polymers that can bind sulfonamide compounds, which represent important drug candidates. Compared to the biological system that utilizes metal coordinated interaction, the imprinted polymer provided pronounced selectivity when hydrogen bond interaction was employed in an organic solvent. Computer simulation of the interaction between the sulfonamide template and functional monomers pointed out that although methacrylic acid had strong interaction energy with the template, it also possessed high non-specific interaction with the solvent molecules of tetrahydrofuran as well as being prone to self-complexation. On the other hand, 1-vinylimidazole was suitable for imprinting sulfonamides as it did not cross-react with the solvent molecules or engage in self-complexation structures.
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| 3. |
- Klein, Michael, 1971, et al.
(författare)
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Synthesis of chiral 1,4-disubstituted-1,2,3-triazole derivatives from amino acids
- 2009
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 14:12, s. 5124-5143
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Tidskriftsartikel (refereegranskat)abstract
- A versatile method for the synthesis of chiral 1,4-disubstituted-1,2,3-triazole derivatives starting from easily accessible naturally occurring D-or L-amino acids as chiral synthons is described. The amino acids were converted into azido alcohols, followed by copper catalyzed [3+2] cycloaddition reactions between the azido alcohols and methyl propiolate and subsequent ester aminolysis with primary and secondary amines furnished the target compounds, which were obtained in excellent yields with no racemization. Docking of selected target compounds shows that the chiral 1,4-disubstituted-1,2,3-triazoles derivatives has the potential of mimicking the binding mode of known purine analogues.
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| 4. |
- Korner, Anna, et al.
(författare)
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Influence of Different Polymer Types on the Overall Release Mechanism in Hydrophilic Matrix Tablets
- 2009
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Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 14:8, s. 2699-2716
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Tidskriftsartikel (refereegranskat)abstract
- The effect of three different types of polymer chain structures on the polymer release from hydrophilic matrix tablets was investigated by comparing a synthetic semi-crystalline linear polymer (PEO), a branched amorphous polysaccharide (dextran) and an amorphous substituted cellulose derivative (HPMC). The polymer release rates for tablets containing mixtures of high and low molecular weight grades in different ratios were determined by using a modified USP II method and a SEC-RI chromatography system. The results showed that independent of polymer type: (i) plots of the release versus time had similar shapes, (ii) the release of long and short polymer chains was equal and no fractionation occurred during the release and (iii) the release rate could be related to the average intrinsic viscosity of the polymer mixtures. This confirms the hypothesis that the release rate can be related to a constant viscosity on the surface of the hydrophilic matrix tablet and that it is valid for all the investigated polymers.
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| 5. |
- Mutulis, Felikss, et al.
(författare)
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Oligomerization of indole derivatives with incorporation of thiols
- 2008
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 13:8, s. 1846-63
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Tidskriftsartikel (refereegranskat)abstract
- Two molecules of indole derivative, e.g. indole-5-carboxylic acid, reacted with one molecule of thiol, e.g. 1,2-ethanedithiol, in the presence of trifluoroacetic acid to yield adducts such as 3-[2-(2-amino-5-carboxyphenyl)-1-(2-mercaptoethylthio)ethyl]-1Hindole-5-carboxylic acid. Parallel formation of dimers, such as 2,3-dihydro-1H,1'H-2,3'-biindole-5,5'-dicarboxylic acid and trimers, such as 3,3'-[2-(2-amino-5-carboxyphenyl) ethane-1,1-diyl]bis(1H-indole-5-carboxylic acid) of the indole derivatives was also observed. Reaction of a mixture of indole and indole-5-carboxylic acid with 2-phenylethanethiol proceeded in a regioselective way, affording 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-1H-indole-5-carboxylic acid. An additional product of this reaction was 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-2,3-dihydro-1H,1'H-2,3'-biindole-5'-carboxylic acid, which upon standing in DMSO-d6 solution gave 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-1H,1'H-2,3'-biindole-5'-carboxylic acid. Structures of all compounds were elucidated by NMR, and a mechanism for their formation was suggested.
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| 6. |
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| 7. |
- Hirsch, Jan, et al.
(författare)
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Synthesis and Molecular Structure of Methyl 4-O-methyl-α-D-glucopyranuronate
- 2005
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Ingår i: Molecules. - 1420-3049 .- 1420-3049. ; 10:1, s. 251-258
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Tidskriftsartikel (refereegranskat)abstract
- A method for the preparation of methyl 4-O-methyl-α-D-glucopyranuronate and its single crystal X-ray structure determination are reported. The molecule adopts an almost ideal 4C1 (OC3) conformation.
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| 8. |
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| 9. |
- Sawaya, Alexandra C H F, et al.
(författare)
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HPLC-ESI-MS/MS of imidazole alkaloids in Pilocarpus microphyllus
- 2008
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Ingår i: Molecules. - Basel, Switzerland : MDPI AG. - 1431-5157 .- 1420-3049. ; 13:7, s. 1518-29
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Tidskriftsartikel (refereegranskat)abstract
- Pilocarpine, an important imidazole alkaloid, is extracted from the leaves of Pilocarpus microphyllus (Rutaceae), known in Brazil as jaborandi and used mainly for the treatment of glaucoma. Jaborandi leaves also contain other imidazole alkaloids, whose pharmacological and physiological properties are unknown, and whose biosynthetic pathways are under investigation. In the present study, a HPLC method coupled with ESI-MS(n) was developed for their qualitative and quantitative analysis. This method permits the chromatographic separation of the imidazole alkaloids found in extracts of jaborandi, as well as the MS/MS analysis of the individual compounds. Thus two samples: leaves of P. microphyllus and a paste that is left over after the industrial extraction of pilocarpine; were compared. The paste was found to contain significant amounts of pilocarpine and other imidazole alkaloids, but had a slightly different alkaloid profile than the leaf extract. The method is suitable for the routine analysis of samples containing these alkaloids, as well as for the separation and identification of known and novel alkaloids from this family, and may be applied to further studies of the biosynthetic pathway of pilocarpine in P. microphyllus.
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