New designs for inhibitors of the NF-κB: DNA binding

We present a series of new inhibitors of the association between nuclear factor kappa B (NF-B) and the corresponding B site in DNA. They were designed using the lead compound 15-deoxy-^12,14 -prostaglandin J₂ (PGJ2), which is a natural product with demonstrated inhibitory efficiency for this system. First, the binding mode of PGJ2 to NF-B was unraveled by GOLD docking calculation. Subsequently, substitutions were made to PGJ2 to optimize its association with NF-B. Care was taken not to strongly increase the reactivity of the new compounds, and to keep the overall shape, size and hydrophilicity of the lead compound, which should render them a similar bioavailability. Molecular mechanics calculations were performed to decide on the suitability of the substitutions, and to evaluate the energies of association with NF-B. Density functional theory calculations were performed also to study the overall reactivity of the substituted drugs towards NF-B. Important general conclusions were obtained, concerning the improvement of these natural inhibitors; namely, a set of rational methodologies were deduced to improve the association between the PGJ2 derivatives and NF-B, and their efficiency demonstrated by generating a set of substituted complexes, some of them with a very much increased affinity for NF-B, opening new doors to enlarge the therapeutic capabilities of this class of drugs.     

Stochastic description of a reaction scheme with autocatalysis and saturation law

We apply the master equation and non-linear Fokker-Planck techniques to a model with autocatalysis and (Michaelis-Menten, Langmuir-Hinshelwood) saturation law and the minimal set of reactive steps for a well posed problem is given.     

Development and validation of a capillary electrophoresis method for the determination of phenothiazines in human urine in the low nanogram per milliliter concentration range using field-amplified sample injection

A capillary zone electrophoresis (CZE) method with ultraviolet-visible detection has been established and validated for the determination of five phenothiazines: thiazinamium methylsulfate, promazine hydrochloride, chlorpromazine hydrochloride, thioridazine hydrochloride, and promethazine hydrochloride in human urine. Optimum separation was obtained on a 64.5 cm x 75 microm bubble cell capillary using a buffer containing 150 mM tris(hydroxymethyl)aminomethane and 25% acetonitrile at pH 8.2, with temperature and voltage of 25 degrees C and 20 kV, respectively. Naphazoline hydrochloride was used as an internal standard. Field-amplified sample injection (FASI) has been applied to improve the sensitivity of the detection. Considering the influence of parameters affecting the on-line preconcentration (nature of preinjection plug, sample solvent composition, injection times, and injection voltage) and due to the significant interactions among them, in this paper we propose for the first time the application of a multivariate approach to carry out the study. The optimized conditions were as follows: preinjection plug of water for 7 s at 50 mbar, electrokinetic injection for 40 s at 6.2 kV, and 32 microm of H3PO4 in the sample solvent. Also, a solid-phase extraction (SPE) procedure is developed to obtain low detection limits and an adequate selectivity for urine samples. The combination of SPE and FASI-CZE-UV allows adequate linearities and recoveries, low detection limits (from 2 to 5 ng/mL), and satisfactory precisions (3.0-7.2% for an intermediate RSD %).     

An Absence of Non-specific Immune Response towards para-Sulphonato-calix[n]arenes

The effects of para-Sulphonato-calix[4]arene, para-Sulphonato-calix[6]arene and para-Sulphonato-calix[8]arene on the activation of NADPH oxidase in neutrophils has been studied. All three molecules do not induce NADPH oxidase activation, and hence do not stimulate neutrophils. Measurement of cell viability demonstrates that these three water-soluble calix[n]arene derivatives are not cytotoxic.     

Cadmium speciation in Arabidopsis thaliana as a strategy to study metal accumulation system in plants

The strategy to identify cadmium deactivation mechanism in Arabidopsis thaliana has been developed using selective and sensitive hyphenated techniques. Cadmium concentrations, in main parts of the plant, were determined by ICP-MS and total amount was found as 0.43-0.44 μg g⁻¹ in leaves and 3.3-3.4 μg g⁻¹ in roots. Speciation of the metal complexes in cells was investigated by SEC-ICP-MS in order to estimate the accumulation process. Phytochelatins, desglycyl-phytochelatins and phytochelatins homologues lacking the N-terminal γ-linked glutamic acid were extracted from plant and were identified by RPLC-ESI-MS. Two-dimensional chromatography allowed to link the metal complexes separated by SEC with isoforms of phytochelatins analyzed by high resolution RPLC and confirm their significant responsibility for metal accumulation. The potential of the cadmium complexes speciation indicates that obtained results could be reliable source of knowledge to confirm the information coming from the well-known genomic sequence of Arabidopsis and to estimate the role of γ-glutamyl transpeptidase in metabolism of glutathione.     

Etudes cristallographique magnétique et par résonance Mössbauer de la variété de haute température du pyrophosphate NaFeP2O7

Single crystals of the high-temperature form of NaFeP₂O₇ have been grown by a flux technique. II-NaFeP₂O₇ crystallizes in the monoclinic $\text{P2}{}_1\text{c}$ space group with lattice parameters: a = 7.298(2) Å, b = 7.874(2) Å, c = 9.536(3) Å, β = 111.85(2)°. The structure refined from 1481 independent reflections leads to R = 0.044 and confirms the work previously published by M. Gabelica-Robert, M. Goreaud, P. Labbe, and B. Raveau (J. Solid State Chem.45, 389, 1982). Magnetic Mössbauer resonance studies have shown the existence of antiferromagnetic ordering with a weak ferromagnetic component below 30 K. The FeO bond is markedly ionic in character due to the highly polarizing power of phosphorus in tetrahedral site.     

Synthesis,properties, and X-ray diffraction study of 4-trifluoromethyl-6-phenyl-2-chloro-3-cyanopyridine

4-Trifluoromethyl-6-phenyl-2-chloro-3-cyanopyridine was synthesized, and its molecular-crystal structure was established. The chlorine atom was replaced by amino, mercapto, thiocyanato, and azido groups. The possibility of the direct amination of 4-trifluoromethyl-6-phenyl-3-cyano-2-pyridone by the action of hexamethylphosphoric triamide (HMPT) was demonstrated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1233–1237, September, 1987.