• 농약과학회지
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• 제11권2호
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• pp.59-66
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• 2007

감수성(SBC) 및 저항성(RBC) 잿빛곰팡이병균(Botrytis cinerea)에 대한 N-phenyl-O-phenylthionocarbamate 유도체들의 살균활성에 대한 3차원적인 구조와 활성과의 관계(3D-QSAR)를 CoMFA와 CoMSIA 방법으로 검토하였다. 최적화 된 CoMFA 모델의 예측성과 상관성이 CoMSIA 모델보다 양호하였으며 ($r^2$ 및 $q^2=CoMFA{\gg}CoMSIA$) SBC 균주에 대한 살균활성 모델이 RBC에 대한 모델보다 양호한 통계값 ($r^2=SBC{\gg}RBC$)을 나타내었다. 또한, CoMFA 모델에서는 정전기장보다 입체장이 큰 영향을 미쳤다. CoMSIA 모델에서는 RBC 및 SBC에 대한 살균활성에 관한 CoMSIA장의 영향은 서로 상이하였으나 수소결합 주게장의 영향은 같았다. 통계적으로 양호한 CoMFA 모델에 의하여 두 균주사이 살균활성에 관한 선택성 요소는 입체장의 차이에 기인하는 것으로 판단된다. 그러므로 N-phenyl 고리상 meta 및 para-치환체의 큰 입체장은 SBC에 대한 살균활성을 향상시킬 것으로 예측되었다.

• 농약과학회지
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• 제11권1호
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• pp.8-17
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• 2007

N-phenylbenzenesulfonamide 및 N-phenyl-2-thienylsulfonamide 유도체(1-34)들의 phenyl 및 theinyl 고리상치환기(R1-R5) 변화에 따른 모잘록병균(Pythium ultimum)의 살균활성에 관한 3차원적인 정량적 구조와 활성과의 관계(3D-QSARs)들을 비교 분자장 분석(CoMFA)과 비교분자 유사성 지수분석(CoMSIA) 방법으로 각각 검토하였다. 전반적으로 CoMSIA 모델들의 통계값은 atom based fit 정렬보다는 field fit 정렬시에 높은 값을 나타내었으나 CoMFA모델의 경우에는 차이가 없었다. 그리고 CoMSIA (FF1) 모델($r_{cv.}^2\;(q^2)=0.674$ 및 $r_{ncv.}^2=0.964$)이 CoMFA (AF5) 모델($r_{cv.}^2\;(q^2)=0.616$ 및 $r_{ncv.}^2=0.930$)보다 상관성과 예측성이 양호하였다. CoMSIA (FF1) 모델의 정보에 따라 살균활성은 분자의 정전기장과 소수성장에 의존적이었다. 또한, CoMSIA (FF3) 모델의 등고도 분석 결과로부터 N-phenyl 고리상 R4-치환기의 친수성과 수소결합 받게로서의 성질인 모잘록병균의 살균활성에 기여할 것으로 예상되었다.

• Bulletin of the Korean Chemical Society
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• 제34권3호
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• pp.899-906
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• 2013

Using generated conformations from docking analysis by Gold algorithm, some 3D-QSAR models; CoMFA and CoMSIA have been created on 39 N-benzoylated phenoxazines and phenothiazines, including their S-oxidized analogues. These molecules inhibit the polymerization of tubulin into microtubules and thus they have been studied for the development of antitumor drugs. Training set for the CoMFA and CoMSIA models using 30 docked conformations gives $q^2$ Leave one out (LOO) values of 0.756 and 0.617, and $r^2$ ncv values of 0.988 and 0.956, respectively. The ability of prediction and robustness of the models were evaluated by test set, cross validation (leave-one-out and leave-ten-out), bootstrapping, and progressive scrambling approaches. The all-orientation search (AOS) was used to achieve the best orientation to minimize the effect of initial orientation of the structures. The docking results confirmed CoMFA and CoMSIA contour maps. The docking and 3D-QSAR studies were thoroughly interpreted and discussed and confirmed the experimental $pIC_{50}$ values.

• Bulletin of the Korean Chemical Society
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• 제31권10호
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• pp.2761-2770
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• 2010

In this study, we have developed QSAR models for a series of 38 piperidine-4-carboxamide CCR5 antagonists using CoMFA, CoMSIA and HQSAR methods. Developed models showed good statistics in terms of $q^2$ and $r^2$ values. Best predictions obtained with standard CoMFA model ($r^2$ = 0.888, $q^2$ = 0.651) and combined CoMSIA model ($r^2$ = 0.892, $q^2$ = 0.665) with electrostatics and H-bond acceptor parameter. The validity of developed models was assessed by test set of 9 compounds, which showed good predictive correlation coefficient for CoMFA (0.804) and CoMSIA (0.844). Bootstrapped analysis showed statistically significant and robust CoMFA (0.968) and CoMSIA (0.936) models. Best HQSAR model was obtained with a $q^2$ of 0.662 and $r^2$ of 0.936 using atom, connection, hydrogen, donor and acceptor as parameters and fragment size (7-10) with optimum number of 6 components. Predictive power of developed HQSAR model was proved by test set and it was found to be 0.728.

• Bulletin of the Korean Chemical Society
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• 제32권5호
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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).

• The Korean Journal of Physiology and Pharmacology
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• 제13권1호
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• pp.55-59
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• 2009

Three dimensional quantitative structure activity relationship between diazabicyclo[4.2.0]octanes and nicotinic acetylcholine receptor($h{\alpha}4{\beta}2$ and $h{\alpha}3{\beta}4$) agonists was studied using comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA). From 11 CoMFA and CoMSIA models, CoMSIA with steric and electrostatic fields gave the best predictive models($q^2=0.926$ and 0.945, ${r^2}_{ncv}=0.983$ and 0.988). This study can be used to develop potent $h{\alpha}4{\beta}2$ receptor agonists with low activity on $h{\alpha}3{\beta}4$ subtype.

• 통합자연과학논문집
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• 제9권3호
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• pp.190-198
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• 2016

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organsincluding the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMSIA) on a series of 2-(indol-5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMSIA models were generated based on atom-by-atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMSIA models were generated using different alignments and the best model yielded across-validated $q^2$ of 0.698 with five components and non-cross-validated correlation coefficient ($r^2$) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMSIA models was found to be $r{^2}_{pred}$ 0.653. The study revealed the important structural features required for the biological activity of the inhibitors and could provide useful for the designing of novel and potent drugs for the inhibition of Xanthine oxidase.

• 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.

• Bulletin of the Korean Chemical Society
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• 제26권12호
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• pp.1941-1945
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• 2005

To raises the possibility of designing effective inhibitors, 3D-QSAR for the inhibition of calcineurin-NFAT signaling by new N-(4-oxo-1(4H)-naphthalenylidene benzenesulfonamide derivatives as inhibitors of intracellular protein-protein interactions were studied using CoMFA and CoMSIA methodology. The three templates, N-(4-oxo-1(4H)-naphthalenylidene)benzenesulfonamide (A), benzenesulfonamide (B) and 4-oxo-1(4H)-naphthalenylidene (C) were selected to improve the statistic of the present 3D-QSAR models. The best models with combination of standard field in CoMFA, and steric field and electrostatic field in CoMSIA derived from the template, B and C, because most of the compounds tend not to be aligned in template A. From the based on the CoMFA and CoMSIA contour maps, the $R_1$ and $R_2$ groups on 4-oxo-1(4H) naphthalenylidene ring are steric favor. The ortho position on the benzenesulfonyl ring is steric disfavor and the meta position is steric favor. In addition, the oxygene atom of carbonyl group will have better inhibition activities as it has a negative charge favor. From these findings, we can conclude that the analyses of the contour maps provided insight into possible modification of molecules for effective inhibitiors.

• 통합자연과학논문집
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• 제9권4호
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• pp.241-248
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• 2016

Corticotropin-releasing factor receptors (CRFRs) activate the hypothalamic-pituitary-adrenal axis, which is an integral part of the fight or flight response to stress. Increase in CRH level is observed in Alzheimer's disease and major depression and hypoglycemia. Here, we report on the relevant physicochemical parameters required for the CRFR inhibitors. Comparative molecular similarity indices analysis (CoMSIA) was performed with the derivatives of 8-substituted-2-aryl-5-alkylaminoquinolinesas CRFR inhibitors. The best predictions were obtained for the best CoMSIA model with a $q^2$ of 0.576 with 6 components and $r^2$ of 0.977. The statistical parameters from the generated CoMSIA models indicated that the data are well fitted and have high predictive ability. CoMSIA contour maps could be useful in the designing of more potent and novel CRFR derivatives.