• Applied Biological Chemistry
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• v.51 no.1
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• pp.38-43
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• 2008

3D-QSARs on the fungicidal activity with N-phenylbenzenesulfonamide and N-phenyl-2-thienylsul-fonamide analogues (1-34) against Fusarium wilt (Fusarium oxysporum) were discussed quantitatively using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods, respectively. Generally, the CoMFA models have better predictability and fitness than the CoMSIA models. The fungicidal activities, according to the information of the optimized CoMF A 2 model $(r^2\;_{cv.}=0.523\;&\;r^2\;_{ncv.}=0.956)$, were dependent on the electrostatic field of the N-phenylbenzenesulfonamide analogues. Therefore, from the results of graphical analyses on the contour maps with the optimized CoMFA 2 model, it is expected that the characters of $R_4-substituents$ on the N-phenyl ring as steric and positive charge favor will contribute to the fungicidal activity against Fusarium wilt.

• Bulletin of the Korean Chemical Society
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• v.30 no.3
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• pp.613-617
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• 2009

3D-QSARs for the inhibition activities against protox by herbicidal 2-N-phenylisoindolin-1-one derivatives were studied quantitatively using CoMFA and CoMSIA methods. The result of the statistical quality of optimized CoMSIA model 2 ($FF:\;{r^2}_{cv.};\;0.973\;&\;{r^2}_{ncv.};\;0.612$) was higher than that of CoMFA model 1 ($AF:\;{r^2}_{cv.};\;0.414\;&\;{r^2}_{ncv.};\;0.909$). Also, the relative contribution of the optimized CoMSIA model 2 showed the steric (24.6%), electrostatic (31.0%), hydrophobic (ClogP, 23.4%) and H-bond acceptor field (21.0%), respectively. From the results of the contour maps, the protox inhibition activities are expected to increase when steric favor and H-bond acceptor favor groups are substituted on $R_2$ position and positive favor group are substituted on $C_2,\;C_3,\;and\;C_5$ atom in phenyl ring of $R_2$ position. And the inhibition activities are expected to increase when hydrophobic favor group is substituted on $C_1,\;C_3$ atom in phenyl ring of $R_2$ position and $C_1$ atom of $R_2$ position and hydrophilic favor groups are substituted on $C_4$ atom in phenyl ring of $R_1$ position and the terminal group of $R_1$ position.

• Applied Biological Chemistry
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• v.50 no.3
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• pp.192-197
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• 2007

3D-QSARs on the fungicidal activity of N-phenylbenzenesulfonamide and N-phenyl-2-thienylsulfonamide analogues (1-37) against Phytophthora blight (Phytophthora capsici) were studied quantitatively using CoMFA and CoMSIA methods. The statistical results of the optimized CoMFA (2) model ($r^2_{cv.}(q^2)$ = 0.692 & $r^2_{ncv.}$= 0.965) show better predictability and fitness than CoMSIA (2) model ($r^2_{cv.}(q^2)$ = 0.796 & $r^2_{ncv.}$= 0.958). The fungicidal activities according to the information of the optimized CoMFA (2) model were dependent upon the steric and electrostatic fields of the molecules. Therefore, from the contribution contour maps of CoMFA (2) model, it is expected that 63% contribution was caused by the steric bulk of meta-substituent ($R_1$) on the S-phenyl ring. Also, the other contribution level of 32.9% was represented by the positive charged $R_4-group$ ($R_1$) on the N-phenyl ring and para-substituent ($R_1$) on the S-phenyl ring. A series of higher active compounds, $R_1$= 3-decyl substituent ($pred.pI_50$= 5.88) etc. were predicted based on the findings.

• YAKHAK HOEJI
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• v.55 no.2
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• pp.98-105
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• 2011

To search the minimum structural requirement of tricyclic isoxazole analogues (1~30) as new class potent antidepressant, thee-dimensional quanti- tative-structure relationship (3D-QSAR) models between substituents ($R_1{\sim}R_5$) of tricyclic isoxazoles and their antidepressant activity against medetomidine-induced loss of righting were performed and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indies analysis (CoMSIA) methods. The correlativity and predictability ($r^2$=0.484 and $q^2$=0.947) of CoMSIA-2 model were higher than those of the rest models. The inhibitory activity against medetomidine-induced loss of righting was dependent on electrostatic field (43.4%), hydrophobic field (35.3%), and steric field (21.2%) of tricyclic isoxazoles. From the CoMSIA-2 contour maps, it is predicted that the antidepressant activity of potent antidepressants against medetomidine-induced loss of righting will be able to increase by the substituents ($R_1{\sim}R_5$) which were in accord with CoMSIA field.

• The Korean Journal of Pesticide Science
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• v.12 no.1
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• pp.18-23
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• 2008

3D-QSAR on the inhibitory activities of 6-bromobenzo-[4,5]imidazo[$1,2{\alpha}$]-pyridin-8,9-diones analogues as substrate molecule were studied quantitatively using CoMFA and CoMSIA methods. The statistical values of CoMFA model was better predictability and fitness than CoMSIA model. The inhibitory activities according to the optimized CoMFA 2 model were dependent on the steric field (90.4%). From the CoMFA contour maps, it is found that the branched side chain as R-group will be directly attached to the carbon atom (ipso carbon) of substituent, the inhibitory activities had expected to increase. The positive charge favor groups were placed in the position between imidazol ring and pyridine ring, the inhibitory activities would increase. And if the groups of liner type will be substituted, hydrophilic favor group would raise inhibitory activities.

• The Korean Journal of Pesticide Science
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• v.9 no.1
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• pp.26-34
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• 2005

3D-QSAR studies for the fungicidal activities against resistance phytophthora blight (RPC; 95CC7303) and sensitive phytophthora blight (Phytopthora capsici) (SPC; 95CC7105) by a series of new 2-alkoxyphenyl-3-phenylthioisoindoline-1-one derivatives (A & B) were studieded using comparative molecular similarity indices analyses (CoMSIA) methodology. From the based on the results, the two CoMSIA models, R5 and S1: as the best models were derivated. The statistical results of the models showed the best predictability and fitness for the fungicidal activities based on the cross- validated value ($q^2=0.714{\sim}0.823$) and non cross-validated, value ($r^2_{ncv.}=0.918{\sim}0.954$), respectively. The model R5 for fungicidal activity of RPC generated from the field fit alignment and combination of electrostatic field, H-bond acceptor field and LUMO molecular orbital field. The model S1 (or S5) for fungicidal activity of SPC generated from the atom based fit alignment and combination of steric field and HOMO molecular orbital field. The models also shows that inclusion of H-bond acceptor field (A) improved the statistical significance of the models. From the based graphical analyses of CoMSIA contribution maps, it was revealed that the novel selective character for fungicidal activities between the two fungi by modify of X-sub-stituent on the N-phenyl group and R-substituent on the S-phenyl group will be able to achivement.

• Journal of Integrative Natural Science
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• v.7 no.4
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• pp.227-233
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• 2014

Caspases, a family of cysteinyl aspartate-specific proteases plays a central role in the regulation and the execution of apoptotic cell death. Activation of caspases-3 stimulates a signaling pathway that ultimately leads to the death of the cell. Hence, caspase-3 has been proven to be an effective target for reducing the amount of cellular and tissue damage. In this work, comparative molecular similarity indices analysis (CoMSIA) was performed on a series of 3,4-dihydropyrimidoindolones derivatives which are inhibitors of caspase-3. The best predictions were obtained for CoMSIA model ($q^2$ = 0.586, $r^2$ = 0.955). The predictive ability of test set ($r^2_{pred}$) was 0.723. Statistical parameters from the generated QSAR models indicated the data is well fitted and have high predictive ability. Our theoretical results could be useful to design novel and more potent caspase-3 derivatives.

• Journal of Integrative Natural Science
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• v.9 no.3
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• pp.177-184
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• 2016

CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils and it regulates the neutrophilic inflammation in the lung diseases. CXCR2 antagonist may reduce the neutrophil chemotaxis and alter the inflammatory response. Hence, in the present study, ligand based Comparative Molecular Similar Indices Analysis (CoMSIA) was performed on a series of CXCR2 antagonist named pyrimidine-5-carbonitrile-6-alkyl derivatives. The optimum CoMSIA model was obtained with statistically significant cross-validated coefficients ($q^2$) of 0.582 and conventional coefficients ($r^2$) of 0.987 with steric, electrostatic, hydrophobic, donor and acceptor fields. The contour maps suggest the important structural modifications and this study can be used to guide the development of potent CXCR2 antagonist.

• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.251-262
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• 2011

Human ether-a-go-go related gene (hERG) potassium channel blockade, an undesirable side effect which might cause sudden cardiac death, is one of the major concerns facing the pharmaceutical industry. The purpose of this study is to develop an in silico QSAR model which uncovers the structural parameters of T-type calcium channel blockers to reduce hERG blockade. Comparative molecular similarity indices analysis (CoMSIA) was conducted on a series of piperazine and benzimidazole derivatives bearing methyl 5-(ethyl(methyl)amino)-2-isopropyl-2-phenylpentanoate moieties, which was synthesized by our group. Three different alignment methods were applied to obtain a reliable model: ligand based alignment, pharmacophore based alignment, and receptor guided alignment. The CoMSIA model with receptor guided alignment yielded the best results : $r^2$ = 0.955, $q^2$ = 0.781, $r^2_{pred}$ = 0.758. The generated CoMSIA contour maps using electrostatic, hydrophobic, H-bond donor, and acceptor fields explain well the structural requirements for hERG nonblockers and also correlate with the lipophilic potential map of the hERG channel pore.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.39 no.4
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• pp.329-335
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• 2013

Three-dimensional quantitative structure-activity relationships (3D-QSARs) models between the substituents with changing groups ($R_1$ & $R_2$) of 4-hydroxybenzyl alcohol (4-HBA) derivatives as substrate molecule and their inhibitory activities against tyrosinase were derived and discussed quantitatively. The optimized CoMSIA FF model showed the best predictability and fitness ($r^2$ = 0.858 & $q^2$ = 0.951). The contour maps of the optimized CoMSIA FF model showed that, the inhibitory activities of the analogues against tyrosinase were expected to increase when hydrophobic (Hy) favor, negative charge (E) favor, steric (S) disfavor and hydrogen bond donor (HD) disfavor groups were substituted at the $R_2$ position. When the hydrogen bond donor (HD) favor groups were substituted at the $R_1$ position, it is predicted that the substituents will be able to increase the inhibitory activity.