• Journal of Integrative Natural Science
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• v.8 no.1
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• pp.40-47
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• 2015

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 ($q^2$) of 0.594 and a non-cross-validated correlation coefficient ($r^2$) 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.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.288-294
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• 2010

Three dimensional quantitative-structure relationships (3D-QSARs) models between structures of phenoxy, phenylthio or benzyloxy substituted quinolone analogues and their antitrypanosomal activity against Chagas disease (Trypanosoma cruzi) were derived and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The optimized CoMFA 1 model ($q^2$=0.528 and $r^2$=0.964) showed the best statistical results. According to the optimized CoMFA 1 model, the antitrypanosomal activities were dependent on the steric (60.0%) and electrostatic (36.2%) factors of quinolone derivatives. From the contour maps, it is predicted that the activity will be increased when sterically favored groups were located in $R_4$ and $R_5$ position and sterically disfavored groups were located in $R_2$ position. Also, the positively charged groups on $R_2$ would be able to increase the antitrypanosomal activities.

• Bulletin of the Korean Chemical Society
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• v.25 no.12
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• pp.1801-1806
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• 2004

Ligand-based quantitative structure-activity relationship (QSAR) studies were performed on indolinones derivatives as a potential inhibitor of the protein tyrosine kinase of fibroblast growth factor receptor (FGFR) by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) implemented in the SYBYL packages. The initial X-ray structure of docked ligand (Su5402) to FGFR was used to minimize the 27 training set molecules using TRIPOS force field. Seven models were generated using CoMFA and CoMSIA with grid spacing 2 ${\AA}$. After the PLS analysis the best predicted CoMSIA model with hydrophobicity, hydrogen bond donor and acceptor property showed that a leave-one out(LOO) cross validated value $({r^2}_{cv})^$ and non-cross validated conventional value $({r^2}_{ncv})^$ are 0.543 and 0.938, respectively.

• Bulletin of the Korean Chemical Society
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• v.34 no.6
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• pp.1643-1650
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• 2013

A non linear QSAR model was constructed on a series of 57 xanthone and curcuminoide derivatives as ${\alpha}$-glucosidase inhibitors by back-propagation neural network method. The neural network architecture was optimized to obtain a three-layer neural network, composed of five descriptors, nine hidden neurons and one output neuron. A good predictive determination coefficient was obtained (${R^2}_{Pset}$ = 86.7%), the statistical results being better than those obtained with the same data set using a multiple regression analysis (MLR). As in the MLR model, the descriptor MATS7v weighted by Van der Waals volume was found as the most important independent variable on the ${\alpha}$-glucosidase inhibitory.

• Journal of Integrative Natural Science
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• v.8 no.3
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• pp.176-183
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• 2015

Corticotropin-releasing actor receptors (CRFRs) activates the hypothalamic pituitary adrenal axis, one of the 2 parts of the fight or flight response to stress. Increased CRH production has is associated with Alzheimer's disease and major depression and hypoglycemia. In this study, we report the important structural and chemical parameters for CRFR inhibitors using the derivatives of 8-substituted-2-aryl-5-alkylaminoquinolines. A 3D QSAR study, Comparative molecular field analysis (CoMFA) was performed. The best predictions were obtained for the best CoMFA model with a $q^2$ of 0.607 with 6 components and $r^2$ of 0.991. The statistical parameters from the generated CoMFA models indicated that the data are well fitted and have high predictive ability. The contour map resulted from the CoMFA models might be helpful in the future designing of novel and more potent CRFR derivatives.

• Journal of Integrative Natural Science
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• v.4 no.4
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• pp.266-272
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• 2011

Focal adhesion kinase (FAK) is a potential target for the treatment of primary cancers as well as prevention of tumor metastasis. To understand the structural and chemical features of FAK inhibitors, we report comparative molecular field analysis (CoMFA) for the series of 7H-pyrrolo(2,3-d)pyrimidines. The CoMFA models showed good correlation between the actual and predicted values for training set molecules. Our results indicated the ligand-based alignment has produced better statistical results for CoMFA ($q^2$ = 0.505, $r^2$ = 0.950). Both models were validated using test set compounds, and gave good predictive values of 0.537. The statistical parameters from the generated 3D-QSAR models were indicated that the data are well fitted and have high predictive ability. The contour map from 3D-QSAR models explains nicely the structure-activity relationships of FAK inhibitors and our results would give proper guidelines to further enhance the activity of novel inhibitors.

• Bulletin of the Korean Chemical Society
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• v.15 no.12
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• pp.1070-1079
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• 1994

Quantitative Structure-Activity Relationship (QSAR) studies are performed for the sets of 40 quinolones and 47 naphthyridines. Net charge, van der Waals volume, polarizability, and dipole moment are empolyed as theoretical descriptors(independent variables) to find the relationship between activity and physicochemical properties such as electrostatic effect, steric effect, and transferability. The results are analyzed by the regression and the factor analysis. It is found that for Gram-negative bacteria, the QSAR of quinolone and naphthyridine are substantially different: to describe the activity, the electrostatic effect is the most important for quinolone, and the steric effect and the transferability for naphthyridine.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.357.1-357.1
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• 2002

Three-dimensional quantitative activity relationship (3D-QSAR) study for a series of arylsulfonylimidazolidinone derivatives with antitumor activity was conducted using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices anaysis (CoMSIA). The in vitro cytotoxicity against human lung carcinoma (A549) exhibited a strong correlation with steric and electrostatic factors of the molecules. (omitted)

• Applied Biological Chemistry
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• v.35 no.1
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• pp.14-22
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• 1992

A series of new N-[1-(benzotriazol-1-yl)aryl]arylamine derivatives were synthesized and their antifungal activities $(pI_{50})$ in vitro against Pyricularia oryzae, Fusarium oxysporum f. sp. sesami, Valsa ceratosperma and Botrytis cinerea were dertermined by the agar medium dilution method. From the results of the quantitative structure-activity relationships $(QSAR_S)$ analysis, $hydrophobicity({\pi})$, $electronic({\Sigma\sigma})$ and molar $refractivity({\Sigma}M_R)$ parameter of X & Y-substituents on the phenyl group were also shown to be important factor in determining the variation in the antifungal activity. 4-Bromo group substituents (1d & 2b) were the most effective compounds and the $half-life(T_{1/2})$ on the hydrolysis of X(1) at netural pH was about 1.5 day. Molecular orbital(MO) functions of substrate compound, linear free energy relationships$(LFER_S)$ on the antifungal reactivity arid the results of molecular design were also discussed.

• Journal of Environmental Health Sciences
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• v.45 no.5
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• pp.457-464
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• 2019

Objectives: Quantitative structure-activity relationship (QSAR) is one of the effective alternatives to animal testing, but its credibility in terms of toxicity prediction has been questionable. Thus, this work aims to evaluate its predictive capacity and find ways of improving its credibility. Methods: Using $TOPKAT^{(R)}$, OECD toolbox, and $Derek^{(R)}$, all of which have been applied world-wide in the research, industrial, and regulatory fields, an analysis of prediction credibility markers including accuracy (A), sensitivity (S), specificity (SP), false negative (FN), and false positive (FP) was conducted. Results: The multi-application of QSARs elevated the precision credibility relative to individual applications of QSARs. Moreover, we found that the type of chemical structure affects the credibility of markers significantly. Conclusions: The credibility of individual QSAR is insufficient for both the prediction of chemical toxicity and regulation of hazardous chemicals. Thus, to increase the credibility, multi-QSAR application, and compensation of the prediction deviation by chemical structure are required.