Synthesis of new azulene derivatives and study of their effect on lipid peroxidation and lipoxygenase activity

The relationship between free radicals and acute or chronic inflammation has been well established. We have previously reported the significant antioxidant activity of the natural azulene derivatives chamazulene and guaiazulene. Furthermore, some synthetic azulene analogues have been found to possess anti-inflammatory activity. In this investigation we report the synthesis of five 3-alkyl or 3-(hydroxy)alkylazulene-1-carboxylic acids and esters, from tropolone, via the corresponding furanone. The synthesised compounds were tested for their effect on the peroxidation of rat hepatic microsomal membrane lipids, applying the 2-thiobarbituric acid test. Their anti-inflammatory activity was evaluated in vitro by the offered inhibition of soybean lipoxygenase. All the tested molecules were found to inhibit lipid peroxidation by 100% at 1 mM. They were also found to considerably inhibit lipoxygenase activity. The above results are discussed in relation to the structure and physicochemical properties of the examined azulene derivatives.     

Surface Tension of the 4-Methyl-2-Pentanone/Ethyl Benzoate Binary System in the Temperature Range from 278.15 to 308.15K

Surface tensions (σ) and densities (ρ) of 4-methyl-2-pentanone/ethyl benzoate binary mixtures have been measured over the entire composition range at 278.15, 288.15, 298.15, and 308.15 K. Values of the excess surface tensions (σ^E) and excess molar volumes (V^E) have been calculated. The σ^E and V^E values were fitted by to the Redlich–Kister polynomial equation and the A_k coefficients have been derived. The standard deviations between the calculated and the experimental excess properties have also been derived. The surface tension values have been further used to calculate the surface entropies (S^S) and surface enthalpies (H^S) per unit surface area. The lyophobicity (β) and the surface mole fractions (x₁^S) of the surfactant 4-methyl-2-pentanone have been derived using the extended Langmuir model. The obtained results are discussed from the viewpoint of the existence of specific interactions between unlike molecules in the bulk region and the surface.     

Direct zonal liquid chromatographic method for the kinetic study of actinomycin-DNA binding

The binding of an anticancer drug (actinomycin D or ACTD) to double-stranded DNA (dsDNA) was studied by means of high-performance liquid chromatography (HPLC). ACTD is an antitumor antibiotic containing one chromophore group and two pentapeptidic lactone cycles that binds dsDNA. Incubations of ACTD with DNA were performed at physiological pH. The complexed and free ligand concentrations of the mixture were quantified at 440 nm from their separation on a size-exclusion chromatographic (SEC) column using the same buffer for the elution and the sample incubation. The DNA and the ACTD-DNA complexes were eluted at the column exclusion volume while the ligand was retained on the support. An apparent binding curve was obtained by plotting the amount emerging at the exclusion column volume against that eluted at free ACTD retention volume. A dissociating effect was evidenced and the binding parameters were significantly different from those obtained at equilibrium by visible absorbance titration. The equilibrium binding parameters determined by absorption spectroscopy were used as starting data in the numerical simulations of the chromatographic process. The results showed a strong dependency of the apparent binding parameters on the reaction kinetics. Finally the comparison of the apparent binding curve obtained from the HPLC experiments and from the numerical simulations permitted an evaluation of the dissociation rate constant (kd = 0.004 s(-1)).     

Antioxidant activity of novel indole derivatives and protection of the myocardial damage in rabbits

Novel indole derivatives containing a triazole moiety (1a-d, 2a-c) were synthesized as lead compounds with interesting pharmacological profiles. Their antioxidant activity was investigated on in vitro non-enzymatic rat hepatic microsomal lipid peroxidation. All compounds showed significant effect in the above assay. The effect depended mainly on the attachment position of the triazole moiety on the indole nucleus. The most potent antioxidant derivatives la, 1c and 1d were tested for their protective ability against the oxidative damage of the myocardium after ischemia-reperfusion, in male rabbits which were subjected to 30 min regional ischemia followed by reperfusion. The tested antioxidant compounds 1a, 1c and 1d were continuously infused for 30 min starting at 10th min of ischemia and lasted at 10th min of reperfusion. The concentration of malondialdehyde (MDA, a marker of lipid peroxidation) and hemodynamic parameters (blood pressure and heart rate) were measured in the baseline, at 20th min of the sustained ischemia, 1st and 20th min of reperfusion. It was found that the examined compounds la, 1c and 1d reduced significantly the level of MDA in rabbits under ischemia-reperfusion and proved to be promising substances for further evaluation of anti-ischemic properties.     

Structural basis for recognition of bacterial cell wall teichoic acid by pseudo-symmetric SH3b-like repeats of a viral peptidoglycan hydrolase

Endolysins are bacteriophage-encoded peptidoglycan hydrolases targeting the cell wall of host bacteria via their cell wall-binding domains (CBDs). The molecular basis for selective recognition of surface carbohydrate ligands by CBDs remains elusive. Here, we describe, in atomic detail, the interaction between the Listeria phage endolysin domain CBD500 and its cell wall teichoic acid (WTA) ligands. We show that 3′O-acetylated GlcNAc residues integrated into the WTA polymer chain are the key epitope recognized by a CBD binding cavity located at the interface of tandem copies of beta-barrel, pseudo-symmetric SH3b-like repeats. This cavity consists of multiple aromatic residues making extensive interactions with two GlcNAc acetyl groups via hydrogen bonds and van der Waals contacts, while permitting the docking of the diastereomorphic ligands. Our multidisciplinary approach tackled an extremely challenging protein–glycopolymer complex and delineated a previously unknown recognition mechanism by which a phage endolysin specifically recognizes and targets WTA, suggesting an adaptable model for regulation of endolysin specificity.

Combining genetic, biochemical and computational approaches, we elucidated the molecular mechanisms underlying the recognition of Listeria wall teichoic acid by bacteriophage-encoded SH3b repeats.     

Synthesis of well‐defined second‐generation dendritic polymers of isoprene (I) and styrene (S): (S2I)3, (SI′I)3, (I″I′I)3, and (I′2I)4

The synthesis of second‐generation (G‐2) dendritic polymers of isoprene (I) and styrene (S) was achieved with anionic polymerization high‐vacuum techniques and by performing the following steps: (1) selective reaction of a living chain with the chlorosilane group of 4‐(chlorodimethylsilyl)styrene (a dual‐functionality compound) to produce a macromonomer, (2) addition of a second living chain (same or different) to the double bond of the macromonomer, (3) polymerization of I with the anionic sites, and (4) reaction of the produced off‐center living species with trichloromethyl silane or tetrachlorosilane (CH₃SiCl₃ or SiCl₄). The combined characterization results showed that the G‐2 dendritic macromolecules synthesized—(S₂I)₃, (SI′I)₃, (I″I′I)₃, (I′₂I)₄—have a high molecular and compositional homogeneity. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1519–1526, 2002     

A new lignan glycoside and other constituents from Cephalaria ambrosioides

A new lignan glycoside, 1,5-dihydroxy-2-(4"-beta-D-glucopyranosyloxy-3"-methoxyphenyl)-6-(4'-hydroxy-3'-methoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, named ambrosidine ([structure: see text]), along with seven known compounds (four iridoids and three hydroxycinnamic esters) were isolated from the roots of Cephalaria ambrosioides. The structures of these compounds were determined by use of NMR and MS techniques and by chemical transformations. The cytotoxic activity of the novel compound [structure: see text] was evaluated against five human solid tumour cell lines.     

Cymodienol and cymodiene: new cytotoxic diarylheptanoids from the sea grass Cymodocea nodosa

The two new diarylheptanoids, cymodienol (1), and cymodiene (2), obtained from specimens of the sea grass Cymodocea nodosa, collected from the coastal areas of central Greece, are the first members of this class isolated from marine organisms. The chemical structures of the two metabolites were assigned on the basis of their NMR and MS spectroscopic data, including information obtained by 1D- and 2D-NMR experiments. Metabolite 2 possesses an unprecedented skeleton that might be biosynthetically related to metabolite 1. Cymodienol (1) was found to exhibit significant cytotoxic activity against two lung cancer cell lines.     

Impact of biological factors on binding media identification in art objects: identification of animal glue in the presence of Aspergillus niger

The materials and especially organic materials used for creation of art objects can be utilized by various microorganisms for their growth and facilitate the microbial colonization of the object. An understanding of the chemical alterations in artefacts caused by the presence of microorganisms can be crucial for correct identification of the materials initially used for the artefact creation--nowadays an important step in restoration and/or art-historical investigation of the art object. The present article describes a model experiment in which we investigated the possible chemical alterations in animal glue films used as substrate for growth of the fungus Aspergillus niger. The sterilized animal glue solution was poured into Petri dishes, inoculated with Aspergillus niger, and subsequently incubated at 15 degrees C for 0, 7, 9, 14, and 28 days. After interruption of incubation, the content of the Petri dish was analyzed for amino acid composition by the GC-MS based method. It was found that the growth of Aspergillus niger on animal glue films did not cause significant changes in the amino acid composition of the film and had no impact on animal glue identification.     

Conductivity Studies of <Emphasis Type="Italic">n</Emphasis>-Tetrabutylammonium Tetraphenylborate in 3-Pentanone in the Temperature Range from 283.15 to 329.15 K

The molar conductivities (Λ) of solutions of n-tetrabutylammonium tetraphenylborate (NBu₄BPh₄) in 3-pentanone have been measured in the temperature range from 283.15 to 329.15 K. The conductance data have been analyzed using the Lee-Wheaton conductivity equation with the distance parameter (a) set at Bjerrum’s pairing distance, and the limiting molar conductivities (Λ_o) and the association equilibrium constants (K _A) have been derived. The limiting ion conductivities (λ_±^o) have been evaluated according to the method of Krumgalz. The λ₊ ^o values have been compared with λ₊ ^o values calculated from the empirical equation of Gill. The thermodynamic functions, Gibbs energy (Δ G _A ^o), enthalpy (Δ H _A ^o) and entropy (Δ S _A ^o) for the process of ion-pair formation as well as the activation energy of the ionic movement (ΔH ^∗) have been evaluated. The obtained results are discussed in terms of ion-ion and ion-solvent interactions.