Earticle

CRTh2 receptor is an important mediator of the inflammatory effects and act as beneficial target for the treatment of asthma, COPD, allergic rhinitis and atopic dermatitis. In the present work, Hologram QSAR studies were conducted on a series of 50 training set CRTh2 antagonists (2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl acetic acids). The best HQSAR model was obtained using atoms, bonds, connections and donor/acceptor as fragment distinction parameter using hologram length 257 and 6 components with fragment size of minimum 7 and maximum 10. Significant cross-validated correlation coefficient (q2=0.786) and non cross-validated correlation coefficients (r2=0. 954) were obtained. The model was then used to evaluate the 15 external test compounds which are not included in the training set and the predicted values were in good agreement with the experimental results (r2 pred=0.739). Contribution map show that presence of C ring and its substituents makes big contributions for activities. The HQSAR model and analysis from the contribution map could be useful for further design of novel structurally related CRTh2 antagonists.

Cysteinyl leukotrienes are inflammatory mediators having important role in pathophysiological conditions such as asthma, allergic rhinitis and have been implicated in a number of inflammatory conditions including cardiovascular and gastrointestinal diseases. Most of the disease regulatory actions of the CysLTs are mediated through CysLT1 receptor. Hence in the present study, homology modeling of CysLT1 was performed because the availability of 3D structure would enhance the development of new drugs for inflammatory diseases. However the templates identified have low sequence identity which increases the complexity of modeling. Hence, homology modeling was performed using single template, multiple templates and also using threading I-TASSER server. The best model was selected based on the validation of the generated models using Ramachandran and ERRAT plot. The model developed could be useful for identifying crucial residues and docking study.

In view of the growing medicinal importance of chromene and its derivatives, the single crystal X-ray diffraction study was carried out for the potential active 4,6-dimethyl-9-phenyl-8,12-dioxa-4,6-diazatetracyclo [8.8.0.02,7.013,18] octadeca- 2(7),13,15,17-tetraene-3,5,11-trione-2-ethoxyphenyl (2E)-but-2-enoate (C18H20N2O5). In the title compound are two molecules exist in the asymmetric unit. It crystallizes in the monoclinic space group P21/c with unit cell dimension a=14.608(3) Å, b=12.845(3) and c= 17.781(4) [alpha & gamma=90o beta=91.233(5)o]. Both pyran and pyran ring of the chromene moiety adopts sofa conformation in the molecule A & B. The crystal structure is stabilized by intramolecular C-H...O hydrogen bond interaction.

The crystal structure of the potential active 2-amino-4-(4-hydroxy-3-methoxyphenyl)-7, 9-dimethyl-5-oxo-4, 5, 6, 7- tetrahydropyrano [2, 3-d] pyrazolo [3, 4-b] pyridine-3-carbonitrile (C21H22N5O6S) has been determined from single crystal X-ray diffraction data. In the title compound crystallizes in the monoclinic space group P-1 with unit cell dimension a=8.1201(9)Å, b=12.2684(4)Å and c= 12.387(2)Å [α=69.573o, β= 12.168o and γ=76.060o]. In the structure the pyrazole, pyridine and pyran are almost coplanar each other. The crystal packing is stabilized by intermolecular C-H...O and NH... O hydrogen bond interaction.

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that has recently emerged as a promising target in drug discovery. It is involved in multiple cellular processes and associated with the pathogenesis of several diseases. A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed on a series of GSK- 3 inhibitors to understand the structural basis for inhibitory activity. Comparative molecular field analysis (CoMFA) method was used to derive 3D-QSAR models. A reliable CoMFA model was developed using ligand-based alignment scheme. The model produced statistically acceptable results with a cross-validated correlation coefficient (q2) of 0.594 and a non-cross-validated correlation coefficient (r2) of 0.943. Robustness of the model was checked by bootstrapping and progressive scrambling analysis. This study could assist in the design of novel compounds with enhanced GSK-3 inhibitory activity.

Novel 2'(β)-methyl-5'-deoxyapiose purine phosphonic acid analogues were designed and synthesized from 2- propanone- 1,3-diacetate. Condensation successfully proceeded from a glycosyl donor 9 under Vorbrüggen conditions. Condensation of aldehyde 14 with Wittig reagent [(diethoxyphosphinyl)methylidene] triphenylphosphorane gave the desired nucleoside phosphonate analogues 15. Ammonolysis and hydrolysis of phosphonates gave the nucleoside phosphonic acid analogue 17 and 19. The synthesized nucleoside analogues were subjected to antiviral screening against HIV-1. The adenine analogue 19 exhibited weak in vitro activities against HIV-1.

To explore effects on each friendship, family, romance, and community in sub-variables of loneliness on academic achievement in science for Y-middle school students, multiple regression analysis is carried out by stepwise method. As the results, I found the following facts. Academic achievement in science for the students was expressed by the following equation. Academic Achievement=48.765+4.012×[Family](t=2.082, p=.039)-3.957×[Romance](t=-3.147, p=.002) +5.281× [Community](t=2.965, p=.003). And each variable value of the explanatory power affecting academic achievement in science for the students is presented in order of community (12.0%), family (6.6%), and romance (6.3%). But the friendship variable is not significant in affecting academic achievement in science.

The physical and optical properties of polymers with 2-fluoroaniline and 4-fluoroaniline added, which can be used for hydrophilic ophthalmic lenses, were investigated in this study. The UV-blocking properties of 2- and 4-fluoroaniline were also investigated by measuring their UV transmissibility. 2- and 4-Fluoroaniline were used as additives for the basic combination of HEMA, 5% AA, and 1% MMA, and the materials were copolymerized with EGDMA as the cross- linking agent and AIBN as the initiator. The refractive index, water content, optical transmittance, tensile strength, and contact angle were measured to evaluate the physical properties of the produced hydrogel lens. The measured physical properties of the hydrogel contact lens produced with the copolymerized polymer showed a refractive index of 1.425-1.436; a water content of 36.95-44.65%; a visual light transmittance of 66.0-81.0%; a tensile strength of 0.138-0.281 kgf; and a contact angle of 55.02-57.87o. The UV transmissibility was significantly reduced, which indicates that 2-fluoroaniline and 4- fluoroaniline have UV-blocking properties. This study showed that 2- and 4-fluoroaniline are expected to be used as UVblocking materials in hydrogel ophthalmic lenses whose physical properties, such as their refractive index and water content, do not change.

Sensing characteristics for porous smart particle based on DBR smart particles were reported. Optically encoded porous silicon smart particles were successfully fabricated from the free-standing porous silicon thin films using ultrasono -method. DBR PSi was prepared by an electrochemical etch of heavily doped p++-type silicon wafer. DBR PSi was prepared by using a periodic pseudo-square wave current. The surface-modified DBR PSi was prepared by either thermal oxidation or thermal hydrosilylation. Free-standing DBR PSi films were generated by lift-off from the silicon wafer substrate using an electropolishing current. Free-standing DBR PSi films were ultrasonicated to create DBR-structured porous smart particles. Three different surface-modified DBR smart particles have been prepared and used for sensing volatile organic vapors. For different types of surface-modified DBR smart particles, the shift of reflectivity mainly depends on the vapor pressure of analyte even though the surfaces of DBR smart particles are different. However huge difference in the shift of reflectivity depending on the different types of surface-modified DBR smart particles was obtained when the vapor pressures are quite similar which demonstrate a possible sensing application to specify the volatile organic vapors.

Thromboxane A2 receptors (TXA2-R) are the G protein coupled receptors localized on cell membranes and intracellular structures and play pathophysiological role in various thrombosis/hemostasis, modulation of the immune response, acute myocardial infarction, inflammatory lung disease, hypertension and nephrotic disease. TXA2 receptor antagonists have been evaluated as potential therapeutic agents for asthma, thrombosis and hypertension. The role of TXA2 in wide spectrum of diseases makes this as an important drug target. Hence in the present study, homology modeling of TXA2 receptor was performed using the crystal structure of squid rhodopsin and night blindness causing G90D rhodopsin. 20 models were generated using single and multiple templates based approaches and the best model was selected based on the validation result. We found that multiple template based approach have given better accuracy. The generated structures can be used in future for further binding site and docking analysis.