C—H⋯N and C—H⋯π interactions in 2‐ethoxy‐4,6‐diphenylpyridine‐3‐carbonitrile

The title compound, C₂₀H₁₆N₂O, has two mol­ecules in the asymmetric unit and the crystal structure shows that the central pyridine ring of each mol­ecule has a flat boat conformation. The terminal C atom in one of the mol­ecules is disordered over two positions, with relative occupancies of 0.594 (14) and 0.398 (14). Intermolecular C—H?N and C—H?π interactions and π–π stacking, along with intramolecular C—H?N and C—H?π interactions, help to stabilize the structure.     

Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen-activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes paragraph sign

Excessive exposure of solar ultraviolet (UV) radiation, particularly its UV-B component, to humans causes many adverse effects that include erythema, hyperplasia, hyperpigmentation, immunosuppression, photoaging and skin cancer. In recent years, there is increasing use of botanical agents in skin care products. Pomegranate derived from the tree Punica granatum contains anthocyanins (such as delphinidin, cyanidin and pelargonidin) and hydrolyzable tannins (such as punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of glucose) and possesses strong antioxidant and anti-inflammatory properties. Recently, we have shown that pomegranate fruit extract (PFE) possesses antitumor promoting effects in a mouse model of chemical carcinogenesis. To begin to establish the effect of PFE for humans in this study, we determined its effect on UV-B-induced adverse effects in normal human epidermal keratinocytes (NHEK). We first assessed the effect of PFE on UV-B-mediated phosphorylation of mitogen-activated protein kinases (MAPK) pathway in NHEK. Immunoblot analysis demonstrated that the treatment of NHEK with PFE (10-40 microg/mL) for 24 h before UV-B (40 mJ/cm(2)) exposure dose dependently inhibited UV-B-mediated phosphorylation of ERKl/2, JNK1/2 and p38 protein. We also observed that PFE (20 microg/mL) inhibited UV-B-mediated phosphorylation of MAPK in a time-dependent manner. Furthermore, in dose- and time-dependent studies, we evaluated the effect of PFE on UV-B-mediated activation of nuclear factor kappa B (NF-kappaB) pathway. Using Western blot analysis, we found that PFE treatment of NHEK resulted in a dose- and time-dependent inhibition of UV-B-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha. Using immunoblot analysis, enzyme-linked immunosorbent assay and electrophoretic mobility shift assay, we found that PFE treatment to NHEK resulted in a dose- and time-dependent inhibition of UV-B-mediated nuclear translocation and phosphorylation of NF-kappaB/p65 at Ser(536). Taken together, our data shows that PFE protects against the adverse effects of UV-B radiation by inhibiting UV-B-induced modulations of NF-kappaB and MAPK pathways and provides a molecular basis for the photochemopreventive effects of PFE.     

Mixed-ligand complexes of copper with some amino-acids and malonate

The mixed-ligand complexes formed by copper(II) with an amino-acid (valine, threonine, isoleucine, aspartic acid, glutamic acid, lysine) and malonic acid have been investigated polarographically and their stability constants determined. The complexes are less stable than the corresponding complexes with oxalic acid instead of malonic, but also exhibit less disproportionation into the simple complexes, because the simple oxalate complexes are more stable than the malonate complexes.     

Thin layer chromatography of 57 metal ions on an inorganic ion-exchanger in mixed solvent systems

Summary Thin layers of stannic arsenate have been used to study the chromatographic behaviour of 57 metal ions in different mixed solvents. Au³⁺, Hg²⁺, UO ₂ ²⁺ , Be²⁺ and Al³⁺ and others can be easily separated from numerous metal ions. Fast quaternary, ternary and binary separations have been also achieved. Important separations are discussed. The effect of pH, duration of heating of ionexchanger plates and layer thickness on the R_f values has been studied and discussed. It is shown that Lederer's equation is also obeyed by thin layers of stannic arsenate, if instead of concentration of Na⁺ ion its activity is taken into consideration.     

Speciation of cationic selenium compounds in Brassica juncea leaves by strong cation-exchange chromatography with inductively coupled plasma mass spectrometry

Strong cation-exchange chromatography (SCX-HPLC) was used in conjunction with inductively coupled plasma mass spectrometry (ICP-MS) to investigate cationic selenium species present in leaf extract of wild-type Brassica juncea supplemented with selenite. Total amount of Se accumulated by the leaves was found to be 352 microg g(-1). Cation-exchange solid-phase extraction (SCX-SPE) was used to pre-concentrate the cationic species present in the leaf extract. Methylselenomethionine (MeSeMet) and dimethylselenoniumproprionate (DMSeP) were synthesized and characterized by electrospray quadrupole time-of-flight MS (ESI-QTOF-MS). Laboratory synthesized and commercially available standards were used in chromatographic studies to identify the Se species in the leaf extract through retention time comparisons and standard addition method. Major cationic selenium species identified in the present study were MeSeMet and methylselenocysteine (MeSeCys) while selenomethionine (SeMet) was found in minor quantities.     

Aldehyde detection by chromogenic/fluorogenic oxime bond fragmentation

Amination of 4-nitrophenol, umbelliferone and 4-methylumbelliferone gave the corresponding oxyamines 1-3. These oxyamines react with aldehydes and ketones to form oximes. In the case of aliphatic aldehydes and electron-poor aromatic aldehydes, the oximes undergo base-catalyzed fragmentation in aqueous buffer in the presence of bovine serum albumin to give the parent phenols, which is the acyclic analog of Kemp's elimination reaction of 5-nitrobenzisoxazole 28. The process can be used as a spectrophotometric assay for formaldehyde under aqueous neutral conditions.     

Synthesis and S-methylation of 2-thioxopyrido[3′,2′:4,5]thieno[3,2-d]-pyrimidin-4(3H)-ones with and without a phase transfer catalyst

A number of 2-thioxopyrido[3′,2′:4,5]thieno[3,2-H]pyrimdin-4(3H-ones (5) have been synthesized by cyclocondensation of 2-carbethoxy-3-amino-4-phenyl-6-substituted-thieno[2,3-b]pyridines (3) with various isothiocyanates. Compounds 5 were S-methylated routinely and the reactions compared under solid-liquid phase transfer conditions to obtain 2-methylthiopyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-^ones (6). The new triheterocyclic pyridothienopyrimidines were prepared with the objective to study their pharmacological properties.     

High performance liquid chromatographic-mass spectrometric assay for the quantitation of BMS-204352 in dog K(3)EDTA plasma

A high performance liquid chromatographic-mass spectrometric (LC/MS) assay was developed and validated for the determination of BMS-204352 in dog K(3)EDTA plasma. A 0.5 mL aliquot of control plasma was spiked with BMS-204352 and internal standard (IS) and buffered with 1 mL of 5 mM ammonium acetate. The mixture was then extracted with 3 mL of toluene. After separation and evaporation of the organic phase to dryness using nitrogen at 40 degrees C, the residue was reconstituted in the mobile phase and 25 microL of the sample were injected onto a Hypersil C(18) column (2 x 50 mm; 3 microm) at a flow rate of 0.5 mL/min. The mobile phase was consisted of two solvent mixtures (A and B). Solvent A was composed of 5 mM ammonium acetate and 0.1% triethylamine in 75:25 v/v water:methanol, pH adjusted to 5.5 with glacial acetic acid, and solvent B was 5 mM ammonium acetate in methanol. A linear gradient system was used to elute the analytes. The mass spectrometer was programmed to admit the de-protonated molecules at m/z 352.7 (IS) and m/z 357.9 (BMS-204352). Standard curves of BMS-204352 were linear (r(2) > or = 0.998) over the concentration range of 0.5-1000 ng/mL. The mean predicted quality control (QC) concentrations deviated less than 5.1% from the corresponding nominal values (ie 4, 80, 400 and 2000 ng/mL); the within- and between-assay precision of the assay were within 5.5% relative standard deviation. Stability of BMS-204352 was confirmed after at least three freeze/thaw cycles and BMS-204532 was stable in dog plasma when stored frozen at or below -20 degrees C for at least 16 weeks in spiked QC samples and for at least 4 1/2 weeks for in vivo study samples. BMS-204352 and IS were stable in the injection solvent at room temperature for at least 24 h. The assay was applied to delineate the pharmacokinetic disposition of BMS-204352 in dogs following a single intravenous dose administration. In conclusion, the assay is accurate, precise, specific, sensitive and reproducible for the pharmacokinetic analysis of BMS-204532 in dog plasma.     

Development and Validation of Kinetic Spectrophotometric Method for the Determination of Losartan Potassium in Pure and Commercial Tablets

A validated kinetic spectrophotometric method has been developed for the determination of losartan potassium in pure and dosage forms. The method is based on oxidation of the losartan potassium with alkaline potassium permanganate at room temperature (25 ± 1 °C). The reaction is followed spectrophotometrically by measuring the increase in absorbance with time at 603 nm, and the initial rate, fixed time (at 12.0 min) and equilibrium time (at 90.0 min) methods are adopted for constructing the calibration graphs. All the calibration graphs are linear in the concentration range of 7.5–60.0 μg mL^?1 and the calibration data resulted in the linear regression equations of n? = ?6.422 × 10^?7 + 1.173 × 10^?5 C, A =3.30 × 10^?4 + 5.28 × 10^?3 C and A = ?2.09 × 10^?2 + 1.05 × 10^?1 C for initial‐rate, fixed time and equilibrium time methods, respectively. The limits of detection for initial rate, fixed time and equilibrium time methods are 0.71, 0.21 and 0.19 μg mL^?1, respectively. The activation parameters such as E_a, ΔH^?, ΔS^?, and ΔG^? are also determined for the reaction and found to be 87.34 KJ mol^?1, 84.86 KJ mol^?1, 50.96 JK^?1 mol^?1 and ?15.10 KJ mol^?1, respectively. The variables are optimized and the proposed methods are validated as per ICH guidelines. The method has been applied successfully to the estimation of losartan potassium in commercial tablets. The performance of the proposed methods was judged by calculating paired t‐ and F‐ values. The analytical results of the proposed methods when compared with those of the reference method show no significant difference in accuracy and precision and have acceptable bias.