Development and validation of a highly sensitive LC‐MS/MS‐ESI method for the determination of bicalutamide in mouse plasma: application to a pharmacokinetic study

A highly sensitive, rapid assay method has been developed and validated for the estimation of bicalutamide in mouse plasma using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the negative‐ion mode. The assay procedure involves extraction of bicalutamide and tolbutamide (internal standard, IS) from mouse plasma with a simple protein precipitation method. Chromatographic separation was achieved using an isocratic mobile phase (0.2% formic acid:acetonitrile, 35:65, v/v) at a flow rate of 0.5 mL/min on an Atlantis dC₁₈ column (maintained at 40 ± 1°C) with a total run time of 3.0 min. The MS/MS ion transitions monitored were m/z 428.9 → 254.7 for bicalutamide and m/z 269.0 → 169.6 for IS. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 1.04 ng/mL and the linearity range extended from 1.04 to 1877 ng/mL. The intra‐ and inter‐day precisions were in the ranges of 0.49–4.68 and 2.62–4.15, respectively. Copyright © 2012 John Wiley & Sons, Ltd.     

Stereoselective total synthesis of (+)-strictifolione and (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one by Prins reaction and olefin cross-metathesis

Prins and olefin cross-metathesis reactions were used as the key steps for the stereoselective total synthesis of (+)-strictifolione and (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one. Removal of MOM protecting groups under neutral conditions using CeCl₃·7H₂O is an attractive addition to the present strategy.     

Generation of aperiodic tilings with fivefold symmetry by the method of intersecting decagons and diffraction from finite size tilings

A method for generating aperiodic tilings with five fold symmetry is discussed here. Basic patterns formed within decagons can be used to fill two dimensional space, by matching such suitable patterns. It appears to be possible to generate perfect tilings without retracing already established coordinates imposing conditions at the initial stages of generating them. Various possible ways to generate tilings, when perfectness is not required, are discussed. The calculated diffraction patterns for some representative finite size tilings are shown. There are subtle differences in the intensities of peaks in the diffraction patterns corresponding to different finite size tilings constructed using intersecting decagons. These effects persist for a larger number of scatterers in weak peaks than in strong peaks. They are unaffected by an introduction of systematic disorder. These effects could be termed as the finite size boundary effects. There are also small shifts in the peak positions owing to the finite size effects. The possibility of formation of large approximate square cells in large tilings is shown.     

Palladium-catalyzed convenient one-pot synthesis of multi-substituted 2-pyrones via transesterification and alkenylation of enynoates

An efficient one-pot protocol for the synthesis of multi-substituted 2-pyrone derivatives from internal alkynes and unactivated alkenes is reported. The methodology involves difunctionalization of internal alkynes by using Pd(II) as a catalyst alongwith X-Phos as ligand via 6-endo transesterification and subsequent alkenylation pathway. Notable features include simple and easily available starting materials, including a range of unactivated alkenes, reduced synthetic steps and mild reaction conditions with high efficiency.     

Synthesis,characterization, DNA cleavage and in vitro antimicrobial activities of copper(II) complexes of Schiff bases containing a 2,4-disubstituted thiazole

Six Cu(II) complexes of Schiff base ligands of arylidene-2-(4-(4-bromo/methoxy-phenyl)thiazol-2-yl) hydrazines have been synthesized, characterized and screened for DNA cleavage and antimicrobial activities. The chemical structures of the complexes were deduced by physicochemical and spectroscopic methods. Elemental analyses indicated that the stoichiometry of the complexes is CuL₂ (L = Schiff base ligand). The DNA cleavage activities of the complexes were evaluated by agarose gel electrophoresis in the presence and absence of oxidant (H₂O₂) and free radical scavenger (DMSO). All the six complexes showed significant nuclease activity in the presence of H₂O₂, and two of the complexes showed moderate nuclease activity even in the absence of oxidant. The complexes did not show nuclease activity in the presence of free radical scavenger. The compounds were tested for activity against selected bacteria and fungi.     

Stereoselective total synthesis of (+)-anamarine via cross-metathesis protocol

A convergent stereoselective total synthesis of (+)-anamarine via cross-metathesis (CM) protocol starting from 2-butyn-1,4-diol and vinyl lactone is reported. Other key features of the strategy include the use of Sharpless asymmetric epoxidation, Sharpless dihydroxylation, and Red-Al reduction.     

Volatile oil composition of Pogostemon heyneanus and comparison of its composition with patchouli oil

The volatile oil of the leaves of Pogostemon heyneanus Benth. (Lamiaceae) was analyzed by GC and GC-MS. Twenty-six components representing 96.0% of the oil were identified. The major components of the oil were acetophenone (51.0%), beta-pinene (5.3%), (E)-nerolidol (5.4%), and patchouli alcohol (14.0%). Comparison of the compositions of the oils of P. heyneanus and P. cablin (Blanco) Benth. (Patchouli oil) showed wide variation between them. Though 13 sesquiterpenes and oxygenated sesquiterpenes were detected in both oils, their concentrations in the oils differed widely. Acetophenone, benzoyl acetone and (E)-nerolidol present in the oil of P. heyneanus were not detected in patchouli oil.     

Immunotherapeutic role of Ag85B as an adjunct to antituberculous chemotherapy

Background

Immunotherapy to enhance the efficiency of the immune response in tuberculosis patients and to eliminate the persisters could be an additional valuable strategy to complement anti-mycobacterial chemotherapy. This study was designed to assess the immunotherapeutic potential of Ag85B as an adjunct to chemotherapy and its effect against active and persister bacteria left after therapy in mouse model of tuberculosis.

Methods

6-8 week old female Balb/c mice were infected with Mycobacterium tuberculosis and treated with chemotherapy or immunotherapy. Protective efficacy was measured in terms of bacterial counts in lungs and spleen. Immune correlates of protection in terms of Th1 and Th2 cytokines were measured by ELISA.

Results

Therapeutic effect of Ag85B was found to be comparable to that of short term dosage of antituberculous drugs (ATDs). The therapeutic effect of ATDs was augmented by the simultaneous treatment with rAg85B and moreover therapy with this protein allowed us to reduce ATD dosage. This therapy was found to be effective even in case of drug persisters. The levels of antigen specific IFNγ and IL-12 were significantly increased after immunotherapy as compared to the basal levels; moreover antigen specific IL-4 levels were depressed on immunotherapy with Ag85B.

Conclusion

We demonstrated in this study that the new combination approach using immunotherapy and concurrent chemotherapy should offer several improvements over the existing regimens to treat tuberculosis. The therapeutic effect is associated not only with initiating a Th1 response but also with switching the insufficient Th2 immune status to the more protective Th1 response.     

Controlled hydrothermal growth of ZnO nanostructures by sequestering the Zn metal ions with the chelating agent EDTA

In the present work, a controlled growth of ZnO nanostructures by manipulating Zn metal ion concentration by the chelating action of ethylene diaminetetra acetic acid in hydrothermal method is studied. EDTA produces metal–chelate complex by the formation of bidentate ligand with Zn²⁺ in the solution and diminishes the reactivity of Zn metal cations. Concentration of EDTA in the mother solution was varied in different ranges like 3, 5 and 10 mM while retaining the zinc metal salt and the NaOH concentration the same. Three different morphologies of wurtzite structured ZnO nanostructures such as nanorods-bunch, separate/discrete uniformly sized hexagonal nanorods and tapered flower petals like shapes are achieved by 3, 5 and 10 mM strengths of EDTA, respectively. The medium concentration 5 mM of EDTA is found to have moderate control over producing ZnO nanostructures of uniform diameter and a high aspect (length to diameter) ratio. An array of vertically aligned free standing ZnO nanorods with uniform spacing is successfully achieved by the addition of 5 mM of EDTA in the mother solution and the same is studied for its fluorescence property at an excitation of 325 nm and it has exhibited a characteristic UV emission of ZnO around 383 nm.