Zinc Chloride Catalyzed Multicomponent Synthesis of Pyrazolopyridocoumarin Scaffolds

An efficient synthesis of a series of pyrazolopyridocoumarins is reported by condensation of 4hydroxycoumarin, benzaldehydes and 1-alkyl-5-amino-pyrazoles in the presence of 10 mol% zinc chloride in ethanol under reflux conditions through one-pot reaction. The significant attraction of this protocol is being a simple procedure, mild reaction condition, and excellent yield. The molecular structure of the compound (4e) is established by single crystal X-ray structure determination

Synthesis of N1 and N2 coumarin substituted 1,​2,​3-​triazole isomers via click chemistry approach

The synthesis of N1 and N2 coumarin substituted 1,​2,​3-​triazole isomers from terminal alkynes, sodium azide, and 4-​bromomethylcoumarins in the presence of triethylamine as a base and CuI as a catalyst in good yield were reported. The mol. structure of compds. and were established by single-​crystal ana

Molecular docking studies of benzimidazopyrimidine and coumarin substituted benzimidazopyrimidine derivatives: As potential human Aurora A kinase inhibitors.

Protein kinases are important drug targets in human cancers, inflammation and metabolic diseases. Docking studies was performed for all the benzimidazopyrimidine and coumarin substituted benzimidazopyridimine derivatives with human Aurora A kinase target (3FDN) employing flexible ligand docking approach by using AutoDock 4.2. All the compounds were found to have minimum binding energy ranging from -6.26 to -9.29 kJ/mol. Among the molecules tested for docking study, 10-(6-Bromo-2-oxo- 2H-chromen-4-ylmethyl)-2-isopropyl-10H-benzo[4,5]imidazo[1,2-a]pyrimidin-4-one (2k) showed minimum binding energy (-9.29 kJ/mol) with ligand efficiency of -0.31. All the ligands were docked deeply within the binding pocket region of 3FDN showing hydrogen bonds with Ala 213 and Asn 261. The docking study results showed that these derivatives are excellent inhibitor of human Aurora A kinase target; and also all these docked compounds have good inhibition constant, vdW + Hbond + desolv energy with best RMSD value

Political ecology of tiger conservation in India: Adverse effects of banning customary practices in a protected area

acceptedVersio

Identificationof Small Molecule Inhibitors of HumanAs(III) S-Adenosylmethionine Methyltransferase(AS3MT)

Arsenic is the most ubiquitous environmental toxin and carcinogen. Long-term exposure to arsenic is associated with human diseases including cancer, cardiovascular disease, and diabetes. Human As(III) S-adenosylmethionine (SAM) methyltransferases (hAS3MT) methylates As(III) to trivalent mono- and dimethyl species that are more toxic and potentially more carcinogenic than inorganic arsenic. Modulators of hAS3MT activity may be useful for the prevention or treatment of arsenic-related diseases. Using a newly developed high-throughput assay for hAS3MT activity, we identified 10 novel noncompetitive small molecule inhibitors. In silico docking analysis with the crystal structure of an AS3MT orthologue suggests that the inhibitors bind in a cleft between domains that is distant from either the As(III) or SAM binding sites. This suggests the presence of a possible allosteric and regulatory site in the enzyme. These inhibitors may be useful tools for future research in arsenic metabolism and are the starting-point for the development of drugs against hAS3MT

Measurement of 67Zn(n,p) 67Cu, 64Zn(n,2n) 63Zn, 89Y(n,&gamma,) 90mY and 89Y(n,2n) 88Y Reaction Cross Sections at the Neutron Energy of 14.54 MeV with Covariance Analysis

The 67Zn(n,p)67Cu, 64Zn(n,2n)63Zn, 89Y(n,&gamma,)90mY and 89Y(n,2n)88Y reaction cross sections relative to the 197Au(n,2n)196Au monitor reaction have been determined at the neutron energy of 14.54 ,± ,0.002 MeV by using the method of activation and off-line &gamma,-ray spectrometry. The neutron energy used was obtained from the 3H(d,n)4He reaction. The covariance analysis was performed by taking the uncertainties arising in various attributes and the correlations between those attributes. The analyzed results from the present measurement were compared with the literature data and evaluated data of various libraries like ENDF/B-VIII, JEFF-3.3, JENDL-4.0 and ROSFOND-2010 libraries as well as with the calculated values based on TALYS-1.9 code

Measurement of 67Zn(n,p) 67Cu, 64Zn(n,2n) 63Zn, 89Y(n,&gamma,) 90mY and 89Y(n,2n) 88Y Reaction Cross Sections at the Neutron Energy of 14.54 MeV with Covariance Analysis

The 67Zn(n,p)67Cu, 64Zn(n,2n)63Zn, 89Y(n,&gamma,)90mY and 89Y(n,2n)88Y reaction cross sections relative to the 197Au(n,2n)196Au monitor reaction have been determined at the neutron energy of 14.54 ,± ,0.002 MeV by using the method of activation and off-line &gamma,-ray spectrometry. The neutron energy used was obtained from the 3H(d,n)4He reaction. The covariance analysis was performed by taking the uncertainties arising in various attributes and the correlations between those attributes. The analyzed results from the present measurement were compared with the literature data and evaluated data of various libraries like ENDF/B-VIII, JEFF-3.3, JENDL-4.0 and ROSFOND-2010 libraries as well as with the calculated values based on TALYS-1.9 code

Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2

In the present study, we used solution combustion synthesis-bismuth oxide (Bi2O3) as catalyst for the simple and efficient synthesis of 1,2-oxazine based derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazoles, 1-arylpiperazine and carbazoles. (4aR,8aR)-4-(4-Methoxyphenyl)-3-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)-4a,5,6,7,8,8a-hexahydro-4H-benzo[e][1,2]oxazine was found to be the most potent compound with a high degree of selectivity in inhibition towards COX2 (1.7 μM) over COX1 (40.4 μM) demonstrating the significance of 1,2-oxazine derivatives in developing COX2 specific inhibitors. Molecular docking analyses demonstrated that an isoleucine residue in the active site of COX1 is responsible for lower affinity to COX1 and increased potency towards COX2. Overall, our study reveals that the new 1,2-oxazine-based small molecules qualify as lead structures in developing COX2-specific inhibitors for anti-inflammatory therapy

Formation of Very Large Conductance Channels by Bacillus cereus Nhe in Vero and GH4 Cells Identifies NheA + B as the Inherent Pore-Forming Structure

The nonhemolytic enterotoxin (Nhe) produced by Bacillus cereus is a pore-forming toxin consisting of three components, NheA, -B and -C. We have studied effects of Nhe on primate epithelial cells (Vero) and rodent pituitary cells (GH4) by measuring release of lactate dehydrogenase (LDH), K+ efflux and the cytosolic Ca2+ concentration ([Ca2+]i). Plasma membrane channel events were monitored by patch-clamp recordings. Using strains of B. cereus lacking either NheA or -C, we examined the functional role of the various components. In both cell types, NheA + B + C induced release of LDH and K+ as well as Ca2+ influx. A specific monoclonal antibody against NheB abolished LDH release and elevation of [Ca2+]i. Exposure to NheA + B caused a similar K+ efflux and elevation of [Ca2+]i as NheA + B + C in GH4 cells, whereas in Vero cells the rate of K+ efflux was reduced by 50% and [Ca2+]i was unaffected. NheB + C had no effect on either cell type. Exposure to NheA + B + C induced large-conductance steps in both cell types, and similar channel insertions were observed in GH4 cells exposed to NheA + B. In Vero cells, NheA + B induced channels of much smaller conductance. NheB + C failed to insert membrane channels. The conductance of the large channels in GH4 cells was about 10 nS. This is the largest channel conductance reported in cell membranes under quasi-physiological conditions. In conclusion, NheA and NheB are necessary and sufficient for formation of large-conductance channels in GH4 cells, whereas in Vero cells such large-conductance channels are in addition dependent on NheC

Production, Secretion and Biological Activity of Bacillus cereus Enterotoxins

Bacillus cereus behaves as an opportunistic pathogen frequently causing gastrointestinal diseases, and it is increasingly recognized to be responsible for severe local or systemic infections. Pathogenicity of B. cereus mainly relies on the secretion of a wide array of toxins and enzymes and also on the ability to undergo swarming differentiation in response to surface-sensing. In this report, the pathogenicity exerted by B. cereus toxins is described with particular attention to the regulatory mechanisms of production and secretion of HBL, Nhe and CytK enterotoxins