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The oxide glass system of the composition (10 – x)SrO–xFe2O3–90V2O5, (x = 0, 2, 4, 6 and 8 mol %) were prepared by a standard melt quenching technique. The amorphous nature of the prepared glass was confirmed using X-ray diffraction technique. The infrared spectra of these glasses were recorded over a continuous spectral range (850–1500 cm–1). The density of prepared sample was obtained by the Archimedes principle. The physical parameters of the glasses were also determined with respect to the composition. Density increases from 3.10 to 3.20 g/cm3, whereas the molar volume decreases with the increase in Fe2O3 concentration. In order to study optical properties, absorption spectra were measured at room temperature. Indirect optical energy band gap, optical dielectric constant, refractive index were calculated from optical energy band gap. The refractive index decreases gradually with the increase in Fe2O3 content due to increase of bridging oxygen’s. For temperatures from 300 to 500 K, the dc conductivity increased with the increasing Fe2O3 content. The dielectric properties like dielectric constant, dielectric loss factor and dielectric loss tangent investigated at the room temperature in the frequency range of 10 kHz to 1 MHz decreases with frequency. The dielectric behavior shows strong frequency as well as composition dependence.

Strontium (Sr) substituted barium zirconate (Ba1-xSrxZrO3, for x = 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0) perovskite nanoceramics were prepared by simple, easy and cost-effective sol-gel auto combustion ...

Iron (Fe) doped barium titanate nanoceramics (BaTi 1- x Fe x O 3 ) were synthesized through sol-gel auto combustion route. The effect of Fe doping on the structural, morphological, ferroelectric and magnetic properties was systematically studied. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopic measurements showed that the synthesized samples have a tetragonal dominant structure with the presence of intermediate hexagonal phase for higher Fe content ( x =0.4 and 0.5). Accurate values of average crystallite size ( D ) and lattice parameter ( a and c ) were calculated by the Williamson-Hall (W-H) analysis and Nelson-Riley extrapolation function (N-R) respectively. The calculated average crystallite size ( D ) of the prepared samples is in the 17–27 nm range. The surface morphology of the grains was examined by field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Compositional stoichiometry was confirmed by energy dispersive spectrum (EDS) analysis. The ferroelectric property was studied by a P-E hysteresis loop. Magnetic and ferroelectric hysteresis loops are strongly influenced by Fe ion doping concentration due to creation of oxygen vacancies. The saturation electric polarization decreases with the increasing of Fe ion doping concentration. The pure BaTiO 3 prepared exhibits diamagnetism. Simultaneously, magnetization of doped compositions is enhanced with increasing of Fe ion concentration. Room temperature ferromagnetism is also observed in Fe doped BaTiO 3 samples. This anomaly in the magnetic behavior can be explained in terms of the changes in the oxidation state exchange interactions of ions such as the Fe 3+ - to - Fe 4+ change induced by oxygen vacancies. A divergence was observed in the temperature dependence of the field cooling (FC) and zero-field cooling (ZFC) magnetization curves, indicating a spin-glass behavior arising from micro-magnetic state, i. e. the mixing of ferromagnetic and antiferro-magnetic phases. The ferromagnetic properties are predominant below 50 K and increases with the Fe doping concentration.

Al 3+ and Cr 3+ co-substituted barium hexaferrite BaCr x Al x Fe 12−2 x O 19 ( x = 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0) nanoparticles were prepared by using sol–gel auto combustion method. X-ray diffraction (XRD) confirmed the formation of M-type hexagonal crystal structure with some additional peaks of Fe 2 O 3 . Various structural parameters such as lattice constants ( a and c ), unit cell volume ( V ), X-ray density ( ρ x ), bulk density ( ρ m ) and porosity ( P ) were determined using XRD data. The lattice constant (a), X-ray density ( ρ x ) and porosity ( P ) decreases with increase in Fe content x . The grain size determined from scanning electron microscopy (SEM) images is in the nanometer range. Fourier transform infrared spectroscopy (FTIR) confirmed the formation of hexagonal ferrite structure for all the calcined samples. The M–H curves recorded at room temperature using pulse field hysteresis loop tracer technique exhibited typical hysteresis loop indicating that the sample exhibits ferromagnetic nature. The large coercivity ( H c ) values indicate the nanocrystalline nature of the present samples. The coercivity ( H c ), saturation magnetization ( M s ), remanence magnetization ( M r ) and magneton number ( n B ) decreases with increase in Al–Cr content x . The dielectric parameters such as dielectric constant ( ɛ ′), dielectric loss ( ɛ ″) and loss tangent ( tan δ ) were measured at room temperature in the frequency range 50 Hz to 5 MHz. All the dielectrical parameters show compositional as a function of frequency dependences. At lower frequencies, it is observed that the dielectric constant ( ɛ ′), dielectric loss ( ɛ ″) and loss tangent ( tan δ ) are high.

The success of bedaquiline as an anti-tubercular agent for the treatment of multidrug-resistant tuberculosis has validated the ATP synthesis pathway and in particular ATP synthase as an attractive target. However, limitations associated with its use in the clinic and the drug–drug interactions with rifampicin have prompted research efforts towards identifying alternative ATP synthesis inhibitors with differentiated mechanisms of action. A biochemical assay was employed to screen AstraZeneca's corporate compound collection to identify the inhibitors of mycobacterial ATP synthesis. The high-throughput screening resulted in the identification of 2,4-diaminoquinazolines as inhibitors of the ATP synthesis pathway. A structure–activity relationship for the quinazolines was established and the knowledge was utilized to morph the quinazoline core into quinoline and pyrazolopyrimidine to expand the scope of chemical diversity. The morphed scaffolds exhibited a 10-fold improvement in enzyme potency and over 100-fold improvement in selectivity against inhibition of mammalian mitochondrial ATP synthesis. These novel compounds were bactericidal and demonstrated growth retardation of Mycobacterium tuberculosis in the acute mouse model of tuberculosis infection.

The key to shortening tuberculosis (TB) drug regimen lies in eliminating the reservoir of non-replicating persistent (NRP) Mycobacterium tuberculosis (Mtb). Pyrazinamide (PZA) is the only known drug used as part of a combination therapy that is believed to kill NRP Mtb and achieve sterilization. PZA is active only under low pH screening conditions. Screening and identification of NRP-active anti-TB compounds are severely limited because compounds are usually inactive under regular assay conditions. In an effort to design novel NRP-active anti-TB compounds, we used pyrazinamide as a core and hybridized it with the fragments derived from marketed drugs. One of these designs, compound 8, was a hybrid with fluoroquinolone. This compound exhibited >10 fold improvement in NRP activity under low pH condition as compared to pyrazinamide and a modest activity (0.8 log10 kill) under nutritionally starved NRP condition. Furthermore, compound 8 was active against fluoroquinolone-resistant strains and did not show any activity in a DNA supercoiling assay (gyrase inhibition), suggesting that its mechanism of action is not that of the parent fluoroquinolone. These results provide a novel avenue in the exploration of new chemotypes that are active against non-replicating Mtb.

In the present study, the molecular interaction between ethanolic extract of drug Piper nigrum with (metal ions) ZnCl2 have been investigated by ultrasonic method. The ultrasonic velocity (U), density (ρ), and viscosity (η) of an ethanolic extract of drug with metal ions of different concentration (number of moles of drug = 1.4018, 2.1027, 2.8036, and 3.5045) and different temperature (T = 308.15, 313.15, 318.15, 323.15, and 333.15) K at 2 MHz have been measured through ultrasonic interferometer. From experimental parameters (ultrasonic velocity (U), density (ρ) and viscosity (η)), various thermoacoustical parameters such as adiabatic compressibility (β), intermolecular free length (Lf), specific acoustic impedance (Z) has been calculated. The change in concentration of drug P. nigrum and varying temperature affects compressibility of solution, which gives idea about molecular interactions in liquid mixtures. Obtained experimental and thermoacoustical parameters are used to investigate the solute–solvent interactions between P. nigrum and ZnCl2 ions which is useful to understand the mechanism of their metabolism in living systems. The conclusion drawn from the ultrasonic investigation is the mixture act as structure breaker and there is a complex formation between ZnCl2 and P. nigrum for the system as a function of concentration and temperature. The results obtained from these studies are helpful for pharmacological applications of drugs, transport of drugs across biological membranes.

Hydrolysis rates for three related methyl α-septanosides were obtained. The septanosides were synthesized via mCPBA epoxidation and methanolysis of d-mannose, d-galactose, and d-glucose-based oxepines. The rate of hydrolysis correlates with the orientation of hydroxyl groups on the septanose ring in a manner analogous to pyranosides.

For regioselective deprotection studies under SPOS conditions the glucosamine derivatives 4ab/4ba, 4ac/4ca and 4ad/4da – with Fmoc/PA, Fmoc/Lev or Fmoc/Alloc, respectively, as temporary ester protecting groups at 3-O and 4-O – were prepared. Fmoc cleavage with triethylamine in 4ab or 4ba led to PA migration, so the Fmoc/PA pair does not permit regioselective access to the vicinal hydroxy groups. Under the same reaction conditions no Lev migration in 4ac/4ca or Alloc migration in 4ad/4da was observed. Lev removal with hydrazinium acetate in 4ac/4ca and Alloc removal with Pd0 and dimedone as nucleophile in 4ad/4da was also not accompanied by Fmoc migration, so the Fmoc/Lev pair and the Fmoc/Alloc pair can be successfully employed for regioselective access to the 3-hydroxy or the 4-hydroxy group, respectively. However, Fmoc cleavage with piperidine in 4ac/4ca led to Lev migration, and the use of a basic nucleophile for Alloc cleavage also led to Fmoc migration in 4ad. 4-O-Fmoc protection was also combined with Nap ether protection in 4ea. These two groups could be readily and regioselectively removed, thus providing another useful pair for temporary protection of vicinal diols.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Conjugate addition of n-butyl amine to d -glucose derived α,β-unsaturated ester 4 afforded β-amino esters 5a,b that on reduction of ester group, 1,2-acetonide deprotection, and reductive amination led to the formation of corresponding N-butyl 1-deoxy- d -gluco-homonojirimycin 2c and N-butyl 1-deoxy- l -ido-homonojirimycin 2d which were found to be selective β-glucosidase inhibitors with an IC50 value in millimolar range.

The intramolecular aminomercuration reaction of sugar-derived beta-hydroxy-gamma-alkenylamines 8a-c undergoes 5-endo-trig cyclization in high yield. The sugar-substituted pyrrolidines thus obtained were elaborated to the synthesis of polyhydroxylated indolizidine alkaloids, namely, castanospermine 1a, 1-epi-castanospermine 1b, and 8a-epi-castanospermine 1c, having promising glycosidase inhibitory activities.

The asymmetric dihydroxylation of a d-glucose derived alpha,beta-unsaturated ester 3 afforded syn vicinal diols in good to high diastereoselectivity. The conversion of these vicinal diols to the corresponding cyclic sulfate, regio-, stereoselective nucleophilic ring opening by sodium azide, and LAH reduction afforded amino heptitols 7a,b that were converted to azepane 1c,d and nojirimycin analogues 2c,d.

The structural and magnetic properties of the polyethylene glycol (PEG) coated cobalt spinel ferrite (CoFe2O4) nanoparticles have been reported in the present study. CoFe2O4 nanoparticles were prepared by sol-gel auto-combustion method using citric acid + ethylene glycol as a fuel. The prepared powder of cobalt ferrite nanoparticles was annealed at 600°C for 6h and used for further study. The structural characterization of CoFe2O4 nanoparticles were carried out by X-ray diffraction technique. The X-ray analysis confirmed the formation of single phase cubic spinel structure. The crystallite size, Lattice constant and X-ray density of the PEG coated CoFe2O4 nanoparticles were calculated by using XRD data. The presence of PEG on CoFe2O4 nanoparticles and reduced agglomeration in the CoFe2O4 nanoparticles were revealed by SEM studies. The magnetic properties were studied by pulse field hysteresis loop tracer technique at a room temperature. The magnetic parameters such as saturation magnetization, remanence magnetization, coercivity etc have been obtained. These magnetic parameters were get decreased by PEG coating.

Structure-energy relationships for a small group of pyranose and septanose mono-saccharide ligands are developed for binding to Concanavalin A (ConA). The affinity of ConA for methyl “manno” β-septanoside 7 was found to be higher than any of the previously reported mono-septanoside ligands. Isothermal titration calorimetry (ITC) in conjunction with docking simulations and quantum mechanics/molecular mechanics (QM/MM) modeling established the specific role of binding enthalpy in the structure–energy relations of ConA bound to natural mono-saccharides and unnatural mono-septanosides. An important aspect in the differential binding among ligands is the deformation energy required to reorganize internal hydroxyl groups upon binding of the ligand to ConA.

Ring closing metathesis of D-glucose derived diene-substrate containing nitrogen functionality followed by asymmetric dihydroxylation afforded sugar substituted dihydroxylated pyrrolidines 8a-c which on 1,2-acetonide deprotection and reductive amination afforded putative uniflorine A 2a and its analogues 2b-c, respectively.

The Johnson-Claisen rearrangement of D-glucose-derived allylic alcohols 5a,b, afforded sugar-substituted gamma,delta-unsaturated ester in high yield. Conversion of the ester group to an azidomethyl group, epoxidation of the double bond and hydrogenation gave pyrrolidine ring skeletons 13a and 13b, which were transformed to tetrahydroxy perhydroaza-azulenes 1a and 1b, respectively. Glycosidase inhibitory activity was also evaluated.

[reaction: see text] The synthesis and evaluation of glycosidase inhibitory activity of polyhydroxylated indolizidine alkaloids namely 2-hydroxy-1-deoxycastanospermine 3a,b and 2-hydroxy-1-deoxy-8a-epi-castanospermine 3c,d is reported. The key step involves the intermolecular 1,3-dipolar cycloaddition of allyl alcohol to d-glucose-derived nitrone 4, followed by tosylation, that afforded four diastereomeric sugar-substituted isoxazolidines 5a-d with the desired regioselectivity. The one-pot conversion of 5a-d to pyrrolidines 8a-d by hydrogenolysis, removal of 1,2-acetonoide functionality, and hydrogenation afforded corresponding target molecules 3a-d.

The Johnson-Claisen rearrangement of D-gluco and L-ido-derived allylic orthoesters afforded gamma,delta-unsaturated ester that on ester reduction, epoxidation, regioselective oxirane opening by sodium azide and hydrogenation led to sugar amino alcohols--immediate precursors for 1-deoxy-homonojirimycin 3a,b, and polyhydroxylated homoazepanes 4a,b. Our synthetic approach and glycosidase inhibitory activity is reported.

The correlative effects of the two sulphydryl inhibitors viz., the mono-and dithiol reagent, alloxan and cobalt chloride, were studied in the fresh water air breathing catfish,Clarias batrachus. Alloxan induced a typical mammalian-like triphasic response and necrobiotic changes in the islet Β-cells. Cobalt chloride elicited a discontinuous hyperglycemia with cytopathological changes in Β-cells following nearly the same sequence as those induced by alloxan. However, the α-cells of cobalt-treated fish showed, unlike those after alloxanization, specific degranulation, vacuolization and nuclear enlargement. The changes in the hepatic glycogen content of two experimental groups were observed to be equal. Both the drugs appeared to be detrimental to the normal islet function and were, thus, overtly or potentially diabetogenic agents to the fish.

Whole cell based screens to identify hits against Mycobacterium tuberculosis (Mtb), carried out under replicating and non-replicating (NRP) conditions, resulted in the identification of multiple, novel but structurally related spiropiperidines with potent antitubercular properties. These compounds could be further classified into three classes namely 3-(3-aryl-1,2,4-oxadiazol-5-yl)-1'-alkylspiro[indene-1,4'-piperidine] (abbr. spiroindenes), 4-(3-aryl-1,2,4-oxadiazol-5-yl)-1'-alkylspiro[chromene-2,4'-piperidine] (abbr. spirochromenes) and 1'-benzylspiro[indole-1,4'-piperidin]-2(1H)-one (abbr. spiroindolones). Spiroindenes showed >= 4 log(10) kill (at 2-12 mu M) on replicating Mtb, but were moderately active under non replicating conditions. Whole genome sequencing efforts of spiroindene resistant mutants resulted in the identification of I292L mutation in MmpL3 (Mycobacterial membrane protein Large), required for the assembly of mycolic acid into the cell wall core of Mtb. MIC modulation studies demonstrated that the mutants were cross-resistant to spirochromenes but not to spiroindolones. This Letter describes lead identification efforts to improve potency while reducing the lipophilicity and hERG liabilities of spiroindenes. Additionally, as deduced from the SAR studies, we provide insights regarding the new chemical opportunities that the spiroindolones can offer to the TB drug discovery initiatives. (C) 2015 Elsevier Ltd. All rights reserved.