• Applied Biological Chemistry
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• 제51권3호
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• pp.171-176
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• 2008

기질 화합물로써 3${\beta}$-Hydroxy-12-oleanen-28-oic acid 유도체(1-30)들과 그들의 protein tyrosine phosphatase(PTP)-1B 저해활성에 관한 비교분자 유사성 지수분석(CoMSIA)보델을 유도하였다. QSAR 모델의 통계 값은 CoMFA>CoMSIA${\geq}$HQSAR>2D-QSAR 모델의 순서로 양호하였다. 최적화된 CoMSIA F1 모델은 grid 3.0${\AA}$과 field fit 정렬조건에서 가장 족은 예측성과 상관성($r^2_{cf}$=0.754 및 $r^2_{ncv}$=0.976)을 나타내었다. 저해 활성에 관한 CoMSIA상의 기여비율(%)은 수소결합 받게장(48.9%), 입체장(25.8%) 및 소수성장(25.4%)의 순서이었다. 그러므로 기질 화합물의 PTP-1B에 대한 저해활성은 $R_4$-치환기의 수소결합 받게 장(A)에 의존적이었다. 등고도 분석 결과로부터 $R_1$-치환기는 수소결합 받게장이 작고 $R_3$-치환기는 입체장이 작으며 그리고 $R_4$-치환기는 수소결합 받게장, 소수성 및 입체장이 큰 치환기가 저해활성을 증가시킬 것으로 예측되었다.

• 농약과학회지
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• 제12권2호
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• pp.111-117
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• 2008

잿빛곰팡이균(Botrytis cinerea)에 대한 N-phenylbenzenesulfonamides 유도체(1-45)들의 살균활성에 관한 비교 분자장 분석(CoMFA)을 정량적으로 검토하였다. 통계적으로 CoMFA 모델의 예측성과 상관성이 비교분자 유사성 지수분석(CoMSIA) 모델보다 월등히 좋았다. 최적화 된 CoMFA I 모델의 통계값은 예측성이 $r^2_{cv.}(or\;q^2)=0.457$ 그리고 상관성이 $r^2_{ncv.}=0.959$이었고 살균활성은 기질 분자들의 입체장(51.9%)과 정전기장(35.6%)에 의존적이었다. 또한 progressive scrambling 분석으로 얻어진 섭동에 대한 감도($d_q^{2'}/dr^2_{yy'}=0.898$)와 예측성($q^2=0.346$ 및 SDEP=0.614)에 의하여 최적의 CoMFA I 모델은 우연 상관성에 의존적이지 않음을 알았다. 그러므로 CoMFA I 모델의 등고도 분석 결과로부터, N-phenyl 고리상 $R_3$ 및 $R_4$-치환기는 입체적으로 크고 $R_1$-치환기로서 S-phenyl 고리상 para-치환기는 입체적으로 작은 치환체가 살균활성에 기여 할 것으로 기대되었으며 최적화 된 CoMFA I 모델은 잿빛곰팡이균에 대한 살균활성을 예측하는데 유용하게 활용될 수 있을 것이다.

• Bulletin of the Korean Chemical Society
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• 제31권5호
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• pp.1355-1360
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• 2010

In order to search new inhibitors against farnesyl protein transferase (FPTase), a series of 2,3-bis-benzylidenesuccinaldehyde derivatives (1-29) were synthesized and their inhibition activities ($pI_{50}$) against FPTase were measured. From based on the reported results that the inhibitory activities of dimers 2,3-bis-benzylidenesuccinaldehydes were higher than those of monomers cinnamaldehydes, 3D-QSARs on FPTase inhibitory activities of the dimers (1-29) were studied quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The statistical qualities of the optimized CoMFA model II ($r^2{_{cv.}}$= 0.693 and $r^2{_{ncv.}}$= 0.974) was higher than those of the CoMSIA model II ($r^2{_{cv.}}$ = 0.484 and $r^2{_{ncv.}}$ = 0.928). The dependence of CoMFA models on chance correlations was evaluated with progressive scrambling analyses. And the inhibitory activity exhibited a strong correlation with steric factors of the substrate molecules. Therefore, from the results of graphical analyses on the contour maps and of predicted higher inhibitory active compounds, it is suggested that the structural distinctions and descriptors that contribute to inhibitory activities ($pI_{50}$) against FPTase will be able to applied new inhibitor design.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.65.2-65.2
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• 2003

88 selective COX-2 inhibitors belonging to three chemical classes (triaryl rings, diaryl cycloalkanopyrazoles, and diphenyl hydrazides) were studied using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Partial least squares analysis produced statistically significant models with q values of 0.84 and 0.79 for CoMFA and CoMSIA, respectively. The key spatial properties were detected by careful analysis of the isocontour maps. The binding energies calculated from flexible docking correlated with inhibitory activities by the least-squares fit method. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.247.2-248
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• 2003

The three-dimensional quantitative structure-activity relationship (3D-QSAR) approach using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) was applied to 62 derivatives known as COX-2 selective inhibitors. Partial least square (PLS) analyses produced good predicted models with q2 value of 0.803 (s=0.285, F=215.401, r2=0.951) and 0.769 (s=0.192, F=245.364, r2=0.980) for CoMFA and CoMSIA, respectively. (omitted)

• Bulletin of the Korean Chemical Society
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• 제34권8호
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• pp.2387-2393
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• 2013

Benzotriazole is an important synthetic auxiliary for potential clinical applications. A series of benzotriazoles as potential antiproliferative agents by inhibiting histone deacetylase (HDAC) were recently reported. Three-dimensional quantitative structure-activity relationship (3D-QSAR), including comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), were performed to elucidate the 3D structural features required for the antiproliferative activity. The results of both ligand-based CoMFA model ($q^2=0.647$, $r^2=0.968$, ${r^2}_{pred}=0.687$) and CoMSIA model ($q^2=0.685$, $r^2=0.928$, ${r^2}_{pred}=0.555$) demonstrated the highly statistical significance and good predictive ability. The results generated from CoMFA and CoMSIA provided important information about the structural characteristics influence inhibitory potency. In addition, docking analysis was applied to clarify the binding modes between the ligands and the receptor HDAC. The information obtained from this study could provide some instructions for the further development of potent antiproliferative agents and HDAC inhibitors.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• 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.

• 약학회지
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• 제55권2호
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• pp.91-97
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• 2011

To search a new anti-depressant agents against para-chloroamphetamine-induced excitation, three dimensional quantitative-structure relationships (3D-QSAR) models between structure of 3a,4-dihydro-3H-[1]-benzopyronao[4,3]isoxazoles (1-30) and thieir inhibitory activity against para-chloroamphetamine-induced excitation were performed and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. From these basis on the findings, the optimized CoMSIA-2F model ($q^2$=0.793 and $r^2$=0.952) showed the best statistical results. And also, it is found that the para-chloroamphetamine inhibitory activity from the optimized CoMSIA-2F model was dependent on steric field (35.2%) and electrostatic field (64.8%) of tricyclic isoxazoles. Particularly, it is predicted that the inhibitory activity against para-chloroamphetamine-induced excitation will be able to increase by the designed compounds from the CoMSIA-2F model.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.186.3-186.3
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• 2003

The three-dimensional quantitative structure-activity relationship (3D-QSAR) study using the comparative molecular field analysis (CoMFA) was performed on indolinones derivatives as an inhibitor of the protein tyrosine kinase of fibroblast growth factor receptor (FGFR). In the training set, twenty-four indolinone derivatives were aligned based on the indole fragment and the steric and electrostatic fields were included in the analysis. The best predicted model showed the cross-validated coefficient (r$^2$$\sub$cv/) of 0.804 and bib-cross validated coefficient (r$^2$) of 0.942. The CoMFA study can be used to predict several new inhibitors of the FGFR.