• 농약과학회지
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• 제11권3호
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• pp.138-143
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• 2007

감수성(SBC) 및 저항성(RBC) 잿빛곰팡이병균(Botrytis cinerea)에 대한 N-phenyl-O-phenylthionocarbamate 유도체들의 선택적인 살균활성에 대한 3차원적인 구조와 활성과의 관계(3D-QSAR)를 CoMFA와 CoMSIA 방법으로 검토하였다 그 결과, 통계적으로 CoMFA 모델(M5)보다 CoMSIA 모델(M7)이 양호하였으며 살균활성의 선택성에 미치는 요소는 CoMSIA 모델(M7)의 정전기장에 의존적이었다. 그러므로 CoMSIA 모델(M7)의 등고도로부터 N-phenyl 고리의 meta-위치에 음하전을 띄는 수소결합 주게에 의하여 선택성이 개선될 것으로 예상되었다.

• 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.

• Applied Biological Chemistry
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• 제48권3호
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• pp.252-257
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• 2005

새로운 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpropionamide 유도체들의 구조 변화에 따른 발아 전, 논피(Echinochloa crus-galli)에 대한 제초활성과의 3D-QSAR 관계를 상이한 정렬방법에 따라 비교 분자장 분석(CoMFA)과 비교분자 유사성 지수분석(CoMSIA) 방법으로 연구하였다. 가장 양호한 3D-QSAR 모델은 atom based fit 정렬과 CoMFA장과 CoMSIA장의 조합 조건에서 유도된 CoMFA 모델(AI-2)과 CoMSIA 모델(AII-4)이었다. CoMFA 및 CoMSIA 등고도로부터 제초활성은 N-phenyl 고리 상 치환기의 구조변화로 개선될 수 있었다.

• 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.

• 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.

• 농약과학회지
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• 제11권3호
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• pp.131-137
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• 2007

상이한 정렬조건에서 imidaclopid 유도체 중, imidazol 고리상 N-치환체(X)들의 벼멸구(Nilaparvata lugens)에 대한 살충활성에 관하여 CoMFA 및 CoMSIA 모델을 유도하고 정량적으로 검토하였다. 두 최적 모델의 예측성($q^2$ 또는 $r_{cv.}^2$)과 상관성($r_{ncv.}^2$)은 field fit (FF) 정렬보다 atom based fit (AF) 정렬조건의 모델이 좋았으며 CoMFA (A5) 모델보다 CoMSIA (A10) 모델이 더 좋았다. 최적의 CoMSIA (A10) 모델로부터 N-치환체(X)들에 의한 살충활성은 주로 정전기장과 수소결합 받게장에 의존적이었다. 그러므로 CoMSIA (A10) 모델의 등고도로부터 benzoyl 고리(X)상 ortho- 위치에는 양전하, carbonyl기의 산소원자 부분에는 음전하가 큰 작용기일수록 그리고 ortho- 및 meta- 위치의 수소결합 받게가 살충활성을 개선하는데 크게 기여할 것으로 예측되었다.

• Bulletin of the Korean Chemical Society
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• 제30권11호
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• pp.2749-2753
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• 2009

Structural characteristics that influence on the insecticidal activity ($pI_{50}$) of 2-(n-octyl)isothiourea analogues (1-45) against the diamondback moth (Plutella xylostella, L.) based on three dimensional quantitative structure activity relationships (3D-QSARs) were discussed quantitatively using a comparative molecular field analysis (CoMFA) and a comparative molecular similarity indeces analysis (CoMSIA) methods. The statistical values of the CoMFA 2 model were better than those of the CoMSIA 1 model. The CoMFA 2 model was the optimized model with the correlativity (the training set: Ave. = 0.104 & PRESS = 0.613) and the predictability (the test set: Ave. = 0.086 & PRESS = 0.096). Insecticidal activities with the optimized CoMFA 2 model were dependent upon steric factors (79.4%) of $R_1-R_3$ substituents. From the analytical results of CoMFA contour maps, it is predicted that the R1 substituent of 1-45 which has a steric favor in a broad space, $R_2\;and\;R_3$ groups with a steric favor in a narrow space and a H-bond donor favor would have better the insecticidal activity.

• Bulletin of the Korean Chemical Society
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• 제27권11호
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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.

• Bulletin of the Korean Chemical Society
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• 제25권10호
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• pp.1525-1530
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• 2004

Mutagen X (MX) exists in our drinking water as the bi-products of chlorine disinfection. Being one of the most potent mutagen, it attracted much attention from many researchers. MX and its analogs are synthesized and modeled by quantitative structure activity relationship (QSAR) methods. As a result, factors affecting this class of compounds have been found to be steric and electrostatic effects. We tried to collect all the data available from the literature. With both CoMFA and CoMSIA various combinations of physiochemical parameters were systematically studied to produce reasonable 3-dimensional models. The best model for CoMFA gave $q^2$ = 0.90 and $r^2$ = 0.97, while for CoMSIA $q^2$ = 0.85 and $r^2$ = 0.94. So the models seem to be reasonable. Unlike previous result of CoMFA, in our case steric parameter alone gave the best statistics. Although the steric contribution was found to be the most important in both CoMFA and CoMSIA, steric parameter along with electrostatic parameter produced slightly better model in CoMSIA. Overall, steric contribution is clearly the most important single factor. However, when we compare chlorine and bromine substitution, chlorine substitution can be more mutagenic. This indicates that other factors such as electrostatic effect also influence the mutagenicity. From the contour maps, steric contribution seems to be focused on rather small area near C6 substituent of the furanone ring, rather than C3 substituent. Therefore the locality of steric contribution can play a significant role in mutagenicity.

• 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).