• Bulletin of the Korean Chemical Society
• /
• v.28 no.2
• /
• pp.200-206
• /
• 2007

Pharmacophore models for lymphocyte-specific protein tyrosine kinase (P56 LCK) were developed using CATALYST HypoGen with a training set comprising of 25 different P56 LCK inhibitors. The best quantitative pharmacophore hypothesis comprises of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic aliphatic and one ring aromatic features with correlation coefficient of 0.941, root mean square deviation (RMSD) of 0.933 and cost difference (null cost-total cost) of 66.23. The pharmacophore model was validated by two methods and the validated model was further used to search databases for new compounds with good estimated LCK inhibitory activity. These compounds were evaluated for their binding properties at the active site by molecular docking studies using GOLD software. The compounds with good estimated activity and docking scores were evaluated for physiological properties based on Lipinski's rules. Finally 68 compounds satisfied all the properties required to be a successful inhibitor candidate.

• Bulletin of the Korean Chemical Society
• /
• v.33 no.9
• /
• pp.2930-2936
• /
• 2012

A three-dimensional pharmacophore hypothesis was developed for atypical antipsychotics in order to map common structural features of highly active compounds by using HipHop in CATALYST program. The pharmacophore hypotheses were generated using 12 compounds as training set and validated using 11 compounds as test set. The most predictive hypothesis (Hypo1) comprises five features viz. two hydrophobic regions, two hydrogen bond acceptor lipid and one aromatic ring. In the absence of information like crystallized structure of 5-$HT_{2A}$ receptor and binding mode of antipsychotics with 5-$HT_{2A}$ receptor, this hypothesis will serve as a potentially valuable tool in the design of novel atypical antipsychotics acting primarily at 5-$HT_{2A}$ and $D_2$ receptors.

• Journal of Integrative Natural Science
• /
• v.10 no.4
• /
• pp.202-208
• /
• 2017

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organs including the liver, gut, lungs, kidney, heart, brain and plasma. It is involved in gout pathogenesis. Hence, in the present study, Hologram based Quantitative Structure Activity Relationship Study was performed on a series of Xanthine Oxidase antagonist named 2-(indol-5-yl) thiazole derivatives. The best HQSAR model was obtained using Atoms, Bonds, Connection, Hydrogen, Chirality and Donor Acceptor as fragment distinction parameter using hologram length 71 and 4 components with fragment size of minimum 2 and maximum 5. Significant cross-validated correlation coefficient ($q^2$= 0.563) and non cross-validated correlation coefficients ($r^2$= 0.967) were obtained. The model was then used to evaluate the six external test compounds and its $r^2{_{pred}}$ was found to be 0.798. Contribution map show that presence of propyl ring in indole thiazole makes big contributions for improving the biological activities of the compounds. We hope that our HQSAR model and analysis will be helpful for future design of xanthine oxidase antagonists.

• YAKHAK HOEJI
• /
• v.31 no.5
• /
• pp.322-329
• /
• 1987

A rapid and sensitive spectrophotometric method has been developed for quantitation of some phenothiazine derivatives (PTZDS). The method depends on the formation of insoluble yellow complexes between PTZDS and picric acid (PCA) in aqueous layer. These complexes are quantitatively extracted from aqueous phase into chloroform. The binding ratio of PTZDS-PCA complexes were presumed as PTZDS-1 to PCA-1 by means of mole ratio and continuous variation methods. The complexes are stable for more than 24hours in chloroform layer at room temperature. Most of compounds associated with pharmaceutical preparation of PTZDS do not interfere with this method. However, chlorpheniramine and diphenhydramine interfere with the riaethod. The binding state of PTZDS-PCA complexes were presumed by IR and $^1$H-NMR spectra as intermolecular hydrogen bonding.

• Bulletin of the Korean Chemical Society
• /
• v.11 no.2
• /
• pp.99-105
• /
• 1990

The Gutmann acceptor number(AN), solvatochromic parameters $({\alpha},{\beta}\;and\;{\pi}^{\ast})$ and hydrogen bonding equilibrium constants (KHB) were determined for three binary systems of methanol with 1,2-dimethoxyethane(DME), 1,2-dichloroethane(DCE) and pyridine (PYD). The solvolysis rate constants of t-butyl chloride, bromide and iodide were also determined in the three binary systems. Solvent properties and solvolysis rates have been discussed in the light of various solvent parameters. Solvolysis of t-butyl halides are most conveniently explained by the two-stage mechanism involving ion-pair intermediate with the ion-pair formation for chloride and ion pair dissociation for iodide as rate limiting.

• Bulletin of the Korean Chemical Society
• /
• v.14 no.4
• /
• pp.457-461
• /
• 1993

Bioconcentration factors (BCF) in fish of organic nonelectrolytes are well correlated by a linear solvation energy relationship (LSER) of the form : log BCF= -0.95 + 4.74 $V_I/100 - 4.39{\beta} + 0.88{\alpha}$ where $V_I$ is the intrinsic solute molecular volume and ${\beta}$ and ${\alpha}$ are the solvatochromic parameters that measure hydrogen bond acceptor basicity and donor acidity of the compound. The LSER model can not only correlate the property with an accuracy comparable to molecular connectivity model but also provide a quantitative informationon on the nature and relative strength of solute-target system interactions affecting the property of interest. Such an information can hardly be obtained from molecular connectivity model.

• Bulletin of the Korean Chemical Society
• /
• v.19 no.6
• /
• pp.642-645
• /
• 1998

The aminolysis reactions of phenylacetyl chlorides with anilines and N,N-dimethylanilines (DMAS) in acetonitrile at -15.0 ℃ are investigated. The magnitude of ρx (= -2.8 ∼ -2.9) and ρy (= 0.9 ∼ 1.3, after correcting for the fall-off), and the negative sign of ρxy (= -0.12) for the reactions with anilines suggest an associative SN2 mechanism. For the reactions with DMAs, the magnitude of these Hammett coefficients increases so that tighter bond making in the transition state (TS) is predicted. A nonlinear Hammett plots obtained for the DMAs with an electron acceptor substituent is interpreted to result from a more advanced degree of leaving group departure to assist closer approach of the bulky DMA in the TS. The normal secondary kinetic isotope effects $(k_H/k_D>1.0)$ involving deuterated anilines suggest partial deprotonation by hydrogen bonding to the departing chloride ion.

• Korean Journal of Metals and Materials
• /
• v.47 no.2
• /
• pp.91-98
• /
• 2009

The titania nanotubular layer for photocatalytic application was synthesized by anodization process in HF solution and the photocatalytic efficiencies of nanotubular film were evaluated by the decomposition rate of aniline blue. In order to facilitate the photocatalytic reaction, the electron acceptors such as potassium bromate, hydrogen peroxide and ammonium persulfate were added to aniline blue solution and the effects of electron acceptors on the dye degradation efficiency were evaluated. The results showed that the photocatalytic efficiency has markedly improved by adding the electron acceptors.

• Journal of Integrative Natural Science
• /
• v.10 no.2
• /
• pp.85-94
• /
• 2017

Fibroblast growth factor receptor (FGFR) belongs to the family of receptor tyrosine kinase. They play important roles in cell proliferation, differentiation, development, migration, survival, wound healing, haematopoiesis and tumorigenesis. FGFRs are reported to cause several types of cancers in humans which make it an important drug target. In the current study, HQSAR analysis was performed on a series of recently reported 1H-Pyrazolo [3,4-b]pyridine derivatives as FGFR antagonists. The model was developed with Atom (A) and bond (B) connection (C), chirality (Ch), hydrogen (H) and donor/acceptor (DA) parameters and with different set of atom counts to improve the model. A reasonable HQSAR model ($q^2=0.701$, SDEP=0.654, NOC=5, $r^2=0.926$, SEE=0.325, BHL=71) was generated which showed good predictive ability. The contribution map depicted the atom contribution in inhibitory effect. A contribution map for the most active compound (compound 24) indicated that hydrogen and nitrogen atoms in the side chains of ring B as well as hydrogen atoms in the side chain of ring C and the nitrogen atom in the ring D contributed positively to the activity in inhibitory effect whereas, the lowest active compound (compound 04) showed negative contribution to inhibitory effect. Thus results of our study can provide insights in the designing potent and selective FGFR kinase inhibitors.

• Journal of Microbiology and Biotechnology
• /
• v.10 no.1
• /
• pp.1-7
• /
• 2000

Bioconversion of fumarate to succinate was anaerobically conduced in a synthetic medium containing glycerol as a hydrogen donor and fumarate as a hydrogen acceptor. We investigated the effects of pH, carbon and nitrogen sources, conversion substrate, and other culture conditions on the production of succinate using a nwely isoloated Enterococcus facalis PKY1. Addition of a variety of carbonates to the medium significantly increasd the rates of production of succinate. The production of succinate and cell growth were relatively satisfactory in the pH range of 7.0-7.6. By using glycerol as a hydrogen donor, high purity succinate was produced with few byproducts. Yeast extract as a sole nitrogen source was the most effective for producing succinalte. As a result, the optimum condition of biconversion was obtained at a medium containing 20g/I glycerol, 50 g/l fumarate, 15 g/l yeast extract, 10 g/l $K_2HPO_4$, 1 g/I NaCl, 50ppm $MgCl_2{\cdot}6H_2O$, 10ppm $FeSo_4{\cdot}7H_2O$, and 5 g/I $Na_2CO_3$ at pH 7.0-7.6. Under the optimum condition, a succinate concentration of 153 g/I was produced in 36 h. The total volumetric production rate and the molar yield of succinate were 4.3 g/l/h and 85%, respectively.