• Proceedings of the PSK Conference
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• 2003.04a
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• pp.250.1-250.1
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• 2003

In this work, we have conducted 3D-QSAR studies on a series of acanthonic acid derivatives that act as COX-2 inhibitors, using two different methods: comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). CoMFA and CoMSIA analysis of twenty five pimarane analogues produced good models with high predictive abilities. (omitted)

• Bulletin of the Korean Chemical Society
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• v.32 no.5
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• pp.1604-1612
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• 2011

We developed three-dimensional quantitative structure activity relationship (3D-QASR) models for 17 adamantyl derivatives as P-glycoprotein (P-gp) inhibitors. Eighteen different partial charge calculation methods were tested to check the feasibility of the 3D-QSAR models. Best predictive comparative molecular field analysis (CoMFA) model was obtained with the Austin Model 1-Bond Charge Correction (AM1-BCC) atomic charge. The 3D-QSAR models were derived with CoMFA and comparative molecular similarity indices analysis (CoMSIA). The final CoMFA model ($q^2$ = 0.764, $r^2$ = 0.988) was calculated with an AM1-BCC charge and electrostatic parameter, whereas the CoMSIA model ($q^2$ = 0.655, $r^2$ = 0.964) was derived with an AM1-BCC charge and combined steric, electrostatic, hydrophobic and HB-acceptor parameters. Leave-five-out (LFO) cross-validation was also performed, which yielded good correlation coefficient for both CoMFA (0.801) and CoMSIA (0.656) models. Robustness of the developed models was checked further with 1000 run bootstrapping analyses, which gave an acceptable correlation coefficient for CoMFA (BS-$r^2$ = 0.997, BS-SD = 0.003) and CoMSIA (BS-$r^2$ = 0.996, BS-SD = 0.018).

• Archives of Pharmacal Research
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• v.27 no.10
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• pp.1001-1008
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• 2004

Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies on 59 cinnamaldehyde analogues as Farnesyl Protein Transferase (FPTase) inhibitors were investigated using comparative molecular field analysis (CoMFA) with the PLS region-focusing method. Forty-nine training set inhibitors were used for CoMFA with two different grid spacings, $2{\AA}\;and\;1{\AA}$ Ten compounds, which were not used in model generation, were used to validate the CoMFA models. After the PLS analysis, the best predictive CoMFA model showed that the cross-validated value $(r^2_{cv})$ and the non-cross validated conventional value$(r^2_{ncv})$ are 0.557 and 0.950, respectively. From the CoMFA contour maps, the steric and electrostatic properties of cinnamaldehyde analogues can be identified and verified.

• The Korean Journal of Pesticide Science
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• v.14 no.1
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• pp.72-77
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• 2010

The minimum structural requirements of R-phenoxy substituents for herbicidal evaluation of O-(2-(R)-phenoxy)-ethyl-N-aralkylcarbamate (1-15) analogues against phytoene desaturase (PDS) based on the three dimensional quantitative structure-activity relationships (3D-QSARs: CoMFA and CoMSIA) were studied quantitatively. The correlativity and predictability ($r^2_{cv.}=0.753$ and $r^2_{ncv.}=0.964$) of the CoMFA 1 model were higher than those of the rest models. The PDS inhibitory activities from the optimized CoMFA 1 model were depend upon the steric field (44.0%), electrostatic field (36.3%), and hydrophobic field (19.6%) of O-(2-(R)-phenoxy)ethyl-Naralkylcarbamate analogues. From the CoMFA contour maps on the structure of the most active compound (5), if it has the steric favor at meta-, para-position on the phenoxy ring, the negative charge favor in meta-position and positive charge favor in the outside part of para-position, the inhibitory activity will be predicted to increase. Also, if ortho-, para-position, and outside of phenoxy ring are hydrophilic favor, and meta-position is hydrophobic favor, it is predicted that the inhibitory activity against PDS will be able to increase.

• 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.27 no.11
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• pp.1741-1746
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• 2006

3D-QSARs on the neuroblocking activities by 1-(6-chloro-3-pyridylmethyl)-2-nitroiminoimidazolidine analogues as agonist at the nicotinic acetylcholine receptor (nAChR) were studied quantitatively using CoMFA and CoMSIA methodologies. The statistical results of CoMFA (A5: $r^2\;_{cv.}\;=\;0.707\;&\;r^2\;_{ncv.}$= 0.986) and CoMSIA model (A3: $r^2\;_{cv.}$ = 0.715 & $r^2\;_{ncv.}$ = 0.961) showed the best predictability and fitness for neuroblocking activity based on the cross-validated value and non-cross validated value. The steric and H-bond acceptor nature of a compound were essential for high activity. The study on 3D-QSARs between substrate molecules and their neuroblocking activities appears to be an useful approach for designing better neuroblocking drug development.

• 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.

• Bulletin of the Korean Chemical Society
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• v.32 no.2
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• pp.645-650
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• 2011

The 3D-QSAR study of 2-arylbenzoxazoles as novel cholesteryl ester transfer protein inhibitors was performed by comparative molecular field analysis (CoMFA), CoMFA region focusing (CoMFA-RF) for optimizing the region for the final PLS analysis, and comparative molecular similarity indices analysis (CoMSIA) methods to determine the factors required for the activity of these compounds. The best orientation was searched by all-orientation search strategy using AOS, to minimize the effect of the initial orientation of the structures. The predictive ability of CoMFARF and CoMSIA were determined using a test set of twelve compounds giving predictive correlation coefficients of 0.886, and 0.754 respectively indicating good predictive power. Further, the robustness and sensitivity to chance correlation of the models were verified by bootstrapping and progressive scrambling analyses respectively. Based upon the information derived from CoMFA(RF) and CoMSIA, identified some key features that may be used to design new inhibitors for cholesteryl ester transfer protein.

• 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.

• Journal of Integrative Natural Science
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• v.8 no.3
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• pp.214-220
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• 2015

Cancer has emerged as one of the leading cause of deaths worldwide. A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed on a series of quinazoline-based anticancer agents. Purpose of the study is to understand the structural basis for their inhibitory activity. Comparative molecular field analysis (CoMFA) technique was employed to develop 3D-QSAR model. Ligand-based alignment scheme was used to generate a reliable CoMFA model. The model produced statistically significant results with a cross-validated correlation coefficient ($q^2$) of 0.589 and a non-cross-validated correlation coefficient ($r^2$) of 0.928. Model was further validated by bootstrapping and progressive scrambling analysis. This study could assist in the design of novel and more potent anticancer agents.