• 약학회지
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• 제55권2호
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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.

• 대한화학회지
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• 제57권1호
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• pp.99-103
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• 2013

The present communication deals with the Pharmacophore modeling, 3D QSAR and docking analysis on series of Pyrimidine derivatives as potential calcium channel blockers. The computational studies showed hydrogen bond donor, hydrogen bond acceptor, and hydrophobic group are important features for calcium channel blocking activity. These studies showed that Pyrimidine scaffold can be utilized for designing of novel calcium channels blockers for CVS disorders.

• Bulletin of the Korean Chemical Society
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• 제34권6호
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• pp.1823-1828
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• 2013

Tetraoxanes (1,2,4,5-tetraoxanes) have been reported to exhibit potent antimalarial activity. In the present study, the three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on a series of tetraoxanes derivatives using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. The best predictive CoMFA model with atom fit alignment resulted in cross-validated coefficient ($q^2$) value of 0.719, non-cross-validated coefficient ($r^2$) value of 0.855 with standard error of estimate (SEE) 0.335. Similarly, the best predictive CoMSIA model was derived with $q^2$ of 0.739, $r^2$ of 0.847 and SEE of 0.344. The generated models were externally validated using test sets. The final QSAR models as well as the information gathered from 3D contour maps should be useful for the design of novel tetraoxanes having improved antimalarial activity.

• Bulletin of the Korean Chemical Society
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• 제26권6호
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• pp.952-958
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• 2005

Angiotensin-converting enzyme (ACE) is known to be primarily responsible for hypertension. Threedimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of 28 ACE inhibitors. The availability of ACE crystal structure (1UZF) provided the plausible biological orientation of inhibitors to ACE active site (C-domain). Alignment for CoMFA obtained by docking ligands to 1UZF protein using FlexX program showed better statistical model as compared to superposition of corresponding atoms. The statistical parameters indicate reasonable models for both CoMFA ($q^2$ = 0.530, $r^2$ = 0.998) and CoMSIA ($q^2$ = 0.518, $r^2$ = 0.990). The 3D-QSAR analyses provide valuable information for the design of ACE inhibitors with potent activity towards C-domain of ACE. The group substitutions involving the phenyl ring and carbon chain at the propionyl and sulfonyl moieties of captopril are essential for better activity against ACE.

• 통합자연과학논문집
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• 제4권4호
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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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• 제27권2호
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• pp.273-276
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• 2006

Three dimensional quantitative structure-activity relationship studies for a series of isatin derivatives as a nonpeptidyl caspase-3 enzyme inhibitor were investigated using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The first approach of non-peptidyl small molecules by 3D QSAR may be useful in guiding further development of potent caspase-3 inhibitors.

• 대한화장품학회지
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• 제40권4호
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• pp.383-390
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• 2014

기질 분자로서 2-[(2,6-dioxocyclohexyl)methyl]cyclohexane-1,3-dione 유도체(1-23)들의 분자 내 치환기($R_1$ 및 $R_2$)가 변화함에 따른 tyrosinase 수용체의 저해활성에 관한 2D-QSAR 모델로부터 다음과 같은 결론을 얻었다. 유도된 최적의 2D-QSAR 모델은 $Obs.pI_{50}=-0.295({\pm}0.031)TDM$ $-0.120({\pm}0.014)DMZ+0.135({\pm}0.050)DMX$. $R_2+6.382({\pm}0.17)$이었으며, 예측성($q^2=0.843$)보다는 상관성($r^2=0.905$)이 큰 모델이었다. Tyrosinase 저해활성은 TDM > $DMX.R_2{\geq}DMZ$ 순으로 영향을 미치었으며, 기질분자의 소수성(ClogP > 0)이 크고, $R_1$-치환기의 입체적 크기가 클수록 더욱 증가하는 경향을 나타내었다. 모델을 분석한 결과, 분자 내 $R_2$-치환기 상 X-축 성분의 쌍극자능률($DMX.R_2$)이 클수록, 그리고 분자 전체의 쌍극자능률(TDM; Total Dipole Moment)과 Z-성분의 쌍극자능률(DMZ; Dipole Moment of Z-Component)이 작을수록 기질분자의 tyrosinase 저해활성이 높아짐을 암시하였다. 따라서 tyrosinase 저해활성은 기질분자 및 $R_2$-치환기의 전자 친화력에 기인한 것으로 예상되었다. 그러므로 저해활성을 증가시키려면 분자 내 극성 그룹을 소수성에 기여하는 비극성 작용기로 대체함이 바람직할 것으로 예측되었다.

• 통합자연과학논문집
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• 제8권3호
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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.

• 통합자연과학논문집
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• 제8권3호
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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.

• Bulletin of the Korean Chemical Society
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• 제33권1호
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• pp.149-152
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• 2012

The (S)-(+)-decursin and its analogues are reported as potent inhibitors of melanin production in B16 murine melanoma cells. In order to understand the factors responsible for potency as well as inhibition of potency of (S)-(+)-decursin and its analogues, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed. Since receptor structures are not available, a pharmacophore model was constructed. Using PHASE, we generated 3 different models and selected the seven-site model, which returned excellent statistical values ($r^2$ = 0.9127, $Q^2$ = 0.6878, Pearson-R = 0.9014). Using the generated pharmacophore model, we screened a natural products library and obtained 4'-epi-decursin as the most related compound. 4'-epidecursin is similar to (S)-(+)-decursin, but shows additional interaction possibilities with tyrosinase. The study thus sheds some light on possibility of developing more potent tyrosinase inhibitors.