• Journal of Integrative Natural Science
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• v.4 no.2
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• pp.91-98
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• 2011

Quantitative structure-activity relationships (QSAR) have been applied for two decades in the development of relationships between physicochemical properties of chemical substances and their biological activities to obtain a reliable statistical model for prediction of the activities of new chemical entities. The fundamental principle underlying the QSAR is that the structural difference is responsible for the variations in biological activities of the compounds. In this work, we developed 3D-QSAR model for a series of 5-Lipoxygenase inhibitors, utilizing comparative molecular field analysis (CoMFA) and Topomer CoMFA methodologies. Our developed models addressed superiority of Topomer CoMFA over CoMFA. The CoMFA model was obtained with $q^2$=0.593, $r^2$=0.939, $Q^2$=0.334 with 6 optimum number of components (ONC). Higher statistical results were obtained with the Topomer CoMFA model ($q^2$=0.819, $r^2$=0.947, ONC=5). Further robustness of developed models was checked with the ANOVA test and it shows F=113 for CoMFA and F=162.4 for Topomer CoMFA model. Contour map analysis indicated that the more requirement of electrostatic parameter for improved potency.

• The Korean Journal of Pesticide Science
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• v.11 no.3
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• pp.138-143
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• 2007

The relationships between three dimensional quantitative structure and activity relationships (3D-QSARs) for the selective fungicidal function between N-phenyl substituents of N-phenyl-O-phenyl-thionocarbamate derivatives analogues and their the fungicidal activities against resistant (RBC) and sensitive (SBC) gray mold (Botrytis cinerea) were studied quantitatively using CoMFA and CoMSIA methods. The statistical values of optimized CoMSIA (M7) model were better ($r^2$ & $q^2=CoMSIA{\gg}CoMFA$) than that of CoMFA (M5) model. And the factor influencing of the selective between the fungicidal activity against RBC and SBC was dependent on electrostatic field of CoMFA (M5) model. Therefore, it is predicted that, from the CoMSIA contour maps of CoMSIA (M7) model, the selectivity will be improved by the H-bond donor that is with negatively charged favored group at meta-position on the N-phenyl ring.

• Applied Biological Chemistry
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• v.48 no.3
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• pp.252-257
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• 2005

Three-dimensional quantitative structure-activity relationships (3D-QSARs) for the herbicidal activities against pre-emergence barnyard grass (Echinochloa crus-galli) by new 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpropion amide derivatives were studied quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodologies. The best CoMFA model (AI-2) and CoMSIA model (AII-4) were derived from an atom based fit alignment and a combination of CoMFA fields. The herbicidal activities from CoMFA and CoMSIA contour maps showed that the activity will be able to be increased according to the substituents variation on the N-phenyl ring.

• The Korean Journal of Pesticide Science
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• v.12 no.2
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• pp.111-117
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• 2008

The comparative molecular field analysis (CoMFA) for the fungicidal activity with N-phenylbenzenesulfonamide analogues (1-45) against gray mold (Botriyts cinerea) were studied quantitatively. The statistical values of CoMFA models had much better predictability and fitness than those of comparative molecular similarity indices analysis (CoMSIA) models. The statistical values of the optimized CoMFA I model were predictablity, $r^2_{cv.}(or\;q^2)=0.457$ and correlation coefficient, $r^2_{ncv.}=0.959$, and their fungicidal activity was dependent on the steric field (52%) and electrostatic field (35.6%) of the substrate molecules. And also, it was found that the optimized CoMFA I model with the sensitivity to perturbation ($d_q^{2'}/dr^2_{yy'}=0.898$) and prediction ($q^2=0.346$ & SDEP=0.614) produced by a progressive scrambling analysis was not dependent on chance correlation. From the results of graphical analyses on the contour maps with the optimized CoMFA I model, it is expected that the $R_3$ and $R_4$-substituents on the N-phenyl ring as steric favor group and para-substituents ($R_1$) on the S-phenyl ring as steric disfavor group will contribute to the fungicidal activity. Therefore, the optimized CoMFA I model should be applicable to the prediction of the fungicidal activities against gray mold.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.219-225
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• 2002

We have performed a 3D-QSAR/CoMFA analysis of the cytotoxic activities of thirty-five 3-arylisoquinoline derivatives against SK-OV-3 tumor cell line. The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r2 as high as 0.841) was obtained through CoMFA.

• The Korean Journal of Pesticide Science
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• v.11 no.2
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• pp.59-66
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• 2007

Three dimensional quantitative structure-activity relationships (3D-QSARs) on the fungicidal activity of N-phenyl-O-phenylthionocarbamate analogues against resistant and sensitive gray mold (Botrytis cinerea) (RBC & SBC) were studied quantitatively using CoMFA and CoMSIA methods. The correlation coefficient and predict- ability of optimized CoMFA model with the atom based fit alignment were better ($r^2$ & $q^2=CoMFA{\gg}CoMSIA$) than that of CoMSIA model. And statistical values of the models on the fungicidal activity against SBC were showed higher ($r^2=SBC{\gg}RBC$) than that of RBC. In CoMFA models, steric field on the activity was more influenced than electrostatic field. And in case of CoMSIA models, the influence of CoMSIA field on the activity against RBC and SBC was differ from each other but the influence of H-bond donor field was same to the two fungi. It is revealed that the selectivity factor with CoMFA model on the fungicidal activity between the two fungi was caused on the difference of steric field. Therefore, it is predicted that the large steric field with meta- and para-substituents on the N-phenyl ring will be improved to the fungicidal activity with SBC.

• The Korean Journal of Pesticide Science
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• v.10 no.3
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• pp.157-164
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• 2006

Three dimensional quantitative structure-activity relationships (3D-QSARs) for the fungicidal activities against Rhizoctonia solani (RS) and Phytophthora capsici (PC) by N-phenyl substituents(X) of N-phenylthionocarbamate derivatives were studied quantitatively using comparative molecular field analysis (CoMFA) methodology based on different alignment approaches. Statistical quality of CoMFA models with field fit alignment were slightly higher than that of atom based fit alignment. The optimized CoMFA models (RS: RF2 & PC: PF2) were derived from field fit alignment and combination of CoMFA fields. And the statistical results of the two models showed the best predictability of the fungicidal activities based on the cross-validated value $q^2$ ($r^2_{cv.}$ =RS: 0.557 & PC: 0.676) and non-cross-validated value ($r^2_{ncv.}$ =RS: 0.954 & PC: 0.968), respectively. The selective fungicidal activities between two fungi were dependence upon the electrostatic field of substrate molecule. Therefore, the fungicidal activities from CoMFA contour maps showed that the fungicidal activity will be able to increased according to the modification of X-substituents on the substrate molecules.

• The Korean Journal of Pesticide Science
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• v.11 no.1
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• pp.8-17
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• 2007

Three-dimensional quantitative structure-activity relationships (3D-QSARs) on the fungicidal activity against damping-off (Pythium ultimum) with N-phenylbenzenesulfonamide and N-phenyl-2-thienylsulfonamide analogues (1-34) were studied quantitatively using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indeces analysis) methodologies. On the whole, the statistical qualities of CoMSIA models with field fit alignment (FF1-FF5) were slightly higher than that of atom based fit alignment (AF1-AF5) but, the deviations of statistical quality between two alignments in case of CoMFA models were slightly lower. The statistical results of CoMFA and CoMSIA model showed that the optimized CoMSIA model (FF1: $r_{cv.}^2\;(q^2)=0.674$ & $r_{ncv.}^2=0.964$) for damping-off is better predictability and fitness for fungicidal activities than CoMFA model (AF5: $r_{cv.}^2\;(q^2)=0.616$ & $r_{ncv.}^2=0.930$). The fungicidal activities according to the information of the CoMSIA (FF1) model were dependence upon the electrostatic and hydrophobic field of the N-phenylbenzene sulfonamide analogues. Therefore, from the results of graphical analyses on the contour maps with CoMSIA (FF3) model, it is expected that the characters of R4-substituent on the N-phenyl ring as hydrophobic and hydrogen bond acceptor will be contributed to the fungicidal activity against damping-off.

• Journal of Integrative Natural Science
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• v.4 no.2
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• pp.99-102
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• 2011

Effect of protonation and deprotonation of ionization compounds is an important application in Comparative molecular field analysis (CoMFA). There are enough information's were reported about different CoMFA applications such as Series design and selection of training set, Geometries and optimizations of molecules, Effect of partial atomic charges, bioactive conformations and alignment, Interaction energy fields, Effects of different grid spacing etc. However limited information's are available about the ionization of compounds. This study aimed at the critical review of about the effects of protonation of ionizable molecules and its impact on the predictability of CoMFA models. We also discussed about previous implications and the things needed to be considered to come for a final conclusion about its impact on CoMFA predictability.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.34 no.2
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• pp.109-115
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• 2008

The comparative molecular field analyses(CoMFA) models between the substituents with changing groups($R_1{\sim}R_4$) of $3{\beta}$-hydroxy-12-oleanen-28-oic acid derivatives as substrate molecule and their inhibitory activities($pI_{50}$) against protein tyrosine phosphatase(PTP)-1B were derived and discussed quantitatively. The optimized CoMFA F1 model have best predictability and fitness($r^2_{cv.}=0.654$ and $r^2_{ncv.}=0.995$). The order of contribution ratio (%) with CoMFA fields on the inhibitory activities was a steric field(53.0%), electrostatic field(36.2%) and hydrophobic field(10.8%). From the analytical results of CoMFA contour maps, the inhibitory activities were dependent on the R4 group in substrate molecules. Particularly, the new active compounds(P1 & P2) with the inhibitory activity against melanin synthesis were expected.