Synthesis,evaluation and docking studies of some 4-thiazolone derivatives as effective lipoxygenase inhibitors

Some promising 4-thiazolone derivatives as lipoxygenase inhibitors were designed, synthesized, characterized and evaluated for anti-inflammatory activity and respective ulcerogenic liabilities. Compounds (1b, 1e, 3b, and 3e) exhibited considerable in vivo anti-inflammatory activity (57.61, 79.35, 75.00, and 79.35%) against carrageenan-induced rat paw edema model, whereas compounds (1e, 3b, and 3e) were found active against the arachidonic acid-induced paw edema model (55.38, 55.38, and 58.46%). The most potent compound (3e) exhibited lesser ulcerogenic liability compared to the standard diclofenac and zileuton. Further, the promising compounds (1e and 3e) were evaluated for in vitro lipoxygenase (LOX; IC₅₀?=?12.98 µM and IC₅₀?=?12.67 µM) and cyclooxygenase (COX) inhibition assay (COX-1; IC₅₀?>?50 µM and, COX-2; IC₅₀?>?50 µM). The enzyme kinetics of compound 3e was evaluated against LOX enzyme and supported by in silico molecular docking and molecular dynamics simulations studies. Overall, the results substantiated that 5-benzylidene-2-phenyl-4-thiazolones are promising pharmacophore for anti-inflammatory activity.     

LC–MS/MS Determination of Antihypertension Drugs in Rat Plasma and Urine: Applications to Pharmacokinetics

A sensitive, rapid and reproducible LC–MS/MS method for the determination of olmesartan (OLM), amlodipine (ALM) and hydrochlorothiazide (HCZ) in rat plasma and urine has been developed and validated. Irbesartan (IRB) was used as an internal standard. The analytes were separated on a Waters XTerra-C₁₈ column using gradient elution with acetonitrile and 10 mM ammonium acetate buffer (pH 3.5, adjusted with acetic acid) at a flow rate of 1.0 mL min^?1. The three analytes were ionized by positive ion electrospray using multiple-reaction monitoring (MRM) mode to monitor precursor?→?product ion transitions m/z 447.31?→?234.97 for OLM, 408.87?→?238.18 for AML and 290.1?→?204.85 for HCZ. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision, and stabilities were all validated over the concentration range 0.4–100 ng mL^?1 for AML, 0.2–100 ng mL^?1 for OLM, 0.1–100 ng mL^?1 for HCZ. The mean concentrations (C_max) are 10.32, 587, and 3.4 for OLM, ALM, and HCZ, respectively, by the oral administration of 15 mg kg^?1 of each analyte.     

Role of phonons in superconductivity

Though the phonon mediated electron-electron interaction has been widely accepted as the cause of superconductivity, yet some doubts have been raised on the basis of the fact that many properties of superconductors are explained by employing a single Einstein frequency without taking a proper account of phonons in the superconductor. In order to check the role of phonons in superconductivity, we involve the whole of the phonon spectra for obtaining superconducting state parameters of seven superconductors, namely Mg, Zn, Be, Cd, A1, T1 and Pb in anisotropic as well as in isotropic phonon models. It has been observed that the electronphonon coupling strength and the transition temperatureT _c exhibit strong directional dependence and are sensitive to the phonons, reaffirming that the phonon mechanism is responsible for superconductivity. The computed values of isotope effect exponent and the interaction strengthN ₀ V also show similar trend, supporting the phonon mechanism.The authors express their sincere gratitude to Prof. C.M. Kachhava for many useful suggestions. They are also highly thankful to Dr. S. C. Jain for his kind cooperation. K. S. S. and R.S. are also thankful to the Principal of the M. S. J. College, Bharatpur for providing the necessary departmental facilities and to the U.G.C., New Delhi, for providing them with the financial assistance for this work.     

Building block syntheses of site-isolated vanadyl groups in silicate oxides

Cross-linking of the cubic silicate building block, Si8O20 with vanadyl chloride leads to porous solids in which a homogeneous dispersion of isolated vanadyl groups is maintained throughout the matrix even at high loadings of vanadium.