Mechanical properties and biocompatibility of in situ enzymatically cross-linked gelatin hydrogels.

Objectives: Gelatin, a degraded collagen, has been widely used as a scaffolding material in tissue engineering applications. In this work, we aimed at the development of in situ, cross-linking, cytocompatible hydrogels by the use of transglutaminase as a cross-linker for potential application in the regeneration of tissues.

Methods: Hydrogels were prepared from gelatin of different concentrations and bloom degree (175 (G175) or 300 (G300) bloom gelatin) and cross-linked with various amounts of microbial transglutaminase (mTG) at 37°C.

New Aspects in the Formulation of Drugs Based on Three Case Studies.

The improvement of pharmaceutical dosage forms, such as tablets, towards drug delivery control and cost efficiency is of great importance in formulation technologies. Here, three examples: in situ coating, freeze casting and protein-based biocomposites are presented that address the above mentioned issues and contribute to further developments in formulation technologies. The in situ coating increases the economic efficiency by saving process steps in comparison to a conventional tableting process and provides a crystalline coating for a tailorable drug delivery rate.

Reliable identification of cross-linked products in protein interaction studies by 13C-labeled p-benzoylphenylalanine.

We describe the use of the (13)C-labeled artificial amino acid p-benzoyl-L-phenylalanine (Bpa) to improve the reliability of cross-linked product identification. Our strategy is exemplified for two protein-peptide complexes. These studies indicate that in many cases the identification of a cross-link without additional stable isotope labeling would result in an ambiguous assignment of cross-linked products.

Synthesis and characterization of novel 1,2,4-triazine derivatives with antiproliferative activity.

A series of novel small molecules with a 1,2,4-triazine scaffold was obtained according to a recently published and highly efficient synthetic route. Screening for antiproliferative and cytotoxic activity revealed distinct anticancer effects against the human leukemia cell line K-562 combined with a remarkable low cytotoxicity. All compounds were in agreement with the 'rule-of-five' claims by Lipinski and calculated logP(calc) values were experimentally confirmed (logP(exp)).

6-aryl-4-oxohexanoic acids: synthesis, effects on eicosanoid biosynthesis, and anti-inflammatory in vivo-activities.

The synthesis of a series of 6-aryl-4-oxohexanoic acids is described: This involves condensation of an appropriate aldehyde (Ia-f) and levulenic acid using catalytic amounts of piperidine and acetic acid in toluene to afford the 6-aryl-4-oxohex-5-enoic acids (IIa-f). The arylidene derivatives (IIa-d) were reduced by hydrogen at room temperature using palladium (10 %/carbon) as catalyst to produce 6-aryl-4-oxohexanoic acids (IIIa-d) as target compounds. In certain instances, the lactone derivative (IVd) was obtained as a low-melting by-product.

Monitoring eicosanoid biosynthesis via lipoxygenase and cyclooxygenase pathways in human whole blood by single HPLC run.

Eicosanoids play an important role as lipid mediators for physiological and pathological processes. Inhibitors of their biosynthesis have been developed as drugs for various diseases with major health political relevance. The search for more efficient inhibitors of eicosanoid formation requires simultaneous monitoring of various metabolic pathways.

A microtiterplate-based screening assay to assess diverse effects on cytochrome P450 enzyme activities in primary rat hepatocytes by various compounds.

During the development of potential drugs it is useful to identify pharmacological and/or toxicological side effects of a compound as early as possible in order to exclude them from further development for reasons of time and cost. Activation or inactivation of members of the cytochrome P450-dependent monooxygenase system (CYP450) might indicate potential undesired effects of a given compound. However, results using CYP450 assay systems are often inconsistent because of different experimental settings.

[Thieno[2,3-c]quinolines - synthesis and biological investigation].

pH-Dependant reduction of the methyl 3-(2-nitrophenyl)thiophene-2-carboxylate (3), obtained by Suzuki cross-coupling of the methyl 3-iodothiophene-2-carboxylate with 2-nitrophenyl boronic acid yields the cyclic hydroxamic acid 4 and the lactam 5, respectively. The lactam 5 is also formed by reacting the compound 2 with pinacolato 2-aminophenylboronate. The 4-chlorothieno[2,3-c]quinoline 6 is formed from the lactam 5 by heating with POCl3/PCl5.

[Benzo[c][2,7]naphthyridines from 2,6-dinor-nifedipine and its dimethyl 2,5-dicarboxylate isomer].

The reaction of 2-nitrobenzaldehyde with methyl propiolate and ammonium acetate in acetic acid yields 2,6-dinor-nifedipine (1a) and the isomeric rac. 1,4-dihydropyridine (DHP) 1b. The DHP 1 are dehydrogenated both chemically and by anodic oxidation using a rotating platinum electrode (RPE) by means of differential pulse voltammetry (DPV) affording the corresponding pyridines 2a, b.

[Isomeric phenanthridines from 1,2-dihydro-5-methyl-2'-nitro-[1,1'-biphenyl]-2,6-dicarboxylic acid esters].

Hydrolysis of the dienamine function of the dihydrobiphenyls 3 leads to a mixture of the tautomers 4A-C (NMR). The structures of the starting material 3a and the products 4cA and 4bC are confirmed by X-ray crystal analysis. The biphenyls 5 are formed by dehydrogenation of 3 with iodine, whereas 4b produced the additional iodinated compound 6.

[Pyrano[3,4-c]quinolines from 1-desaza--oxa-nifedipine].

Pyrano[3,4-c]quinolines from 1-desaza-1-oxa-nifedipine The reaction of the 1,5-diketone 1 with acetic anhydride/acetic acid in the presence of zinc chloride yields the 1-desaza-1-oxa-nifedipine 2 and the annulated lactone 3 as a by-product. The structures of 2 and 3 are confirmed by X-ray structure analysis. The pH-dependent reduction of the nitro group from 2 leads to the pyrano[3,4-c]quinolines 4Aa, b by ring closure.

[Pyridazino(3,4-c)quinolines and pyridazino(4,5-c)quinolines--synthesis and investigation of lipoxygenase inhibition].

The cyclic hemiketone acetal 6 reacts with hydrazine in tert-butanol to yield the 1-amino-2,3-dihydro-2-hydroxy-pyrrole 7, while in acetic acid a mixture of the 1-amino-pyrrole 8 and the 1,4-dihydropyridazine 9 is obtained. The X-ray crystal structure of 9 shows a boat conformation flattened about N-1 with respect to nifedipine. Removing the boc-group of 9 gives the tautomeric 2,5-dihydropyridazine 13.

[Pyrrolo(2,3-c)quinolines and pyrrolo(3,4-d)quinolines--synthesis and investigation of lipoxygenase inhibition].

The Paal-Knorr synthesis of the cyclic hemiketonacetal 4 yields the pyrrole-2,4-dicarboxylic acid diesters 1c and 7 via the cyclic hemiaminals 5 and 6; while the pyrrole-2-carboxylic acid ester 9 is formed from the 1,4-diketon 10. Under reducing conditions 1c and their 4-carboxylic acid 8 give the pyrrolo[3,4-c]quinoline carboxylic acid ester 2a; the cyclic hydroxamic acid 11 and the lactam 12 of the pyrrolo[2,3-c]quinoline type are obtained from compound 9. The isomeric compounds of the pyrrolo[3,4-c]quinoline series 16, 17 and 18, respectively, are synthesized from the pyrroles 14 and 15; the cyclic hemiacetal 13 was used as educt.

Lipoxygenase inhibitors, Part 6. Synthesis of new tetrahydropyrazine and other heterocyclic compounds by reaction of hydrazonoyl chlorides.

Cyclization reactions of alpha-ketoarylhydrazonoyl chlorides with various dinucleophiles lead to new 1,4-benzothiazine, quinoxaline, tetrahydropyrazine, thiazole, and thiadiazoline derivatives of methyl butanoate or methyl 5-oxopentanoate. The inhibition of 5-lipoxygenase (LO) was determined by monitoring the leukotriene B4 (LTB4) formation of human polymorphonuclear leukocytes (PMNL). The IC50 values for the most active compounds with an arylhydrazone structure were found to lie between 0.

[Lipoxygenase inhibitors. IV. Synthesis and cyclization reactions of open-chain N1-aryl-substituted amidrazones].

alpha-Carbonyl carboxylic acid arylhydrazonochlorides obtained by Japp-Klingemann reaction are the starting substances for the synthesis of alpha-carbonyl carboxylic acid arylhydrazonoamides, -esters and -thioesters. The inhibiting activity of these compounds against 15- and 5-lipoxygenase is described. Reactions of derivatives of amidrazones with formaldehyde give triazole, triazoline and unexpected benzotriazepine derivatives.