• 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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• 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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• 제25권12호
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• pp.1801-1806
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• 2004

Ligand-based quantitative structure-activity relationship (QSAR) studies were performed on indolinones derivatives as a potential inhibitor of the protein tyrosine kinase of fibroblast growth factor receptor (FGFR) by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) implemented in the SYBYL packages. The initial X-ray structure of docked ligand (Su5402) to FGFR was used to minimize the 27 training set molecules using TRIPOS force field. Seven models were generated using CoMFA and CoMSIA with grid spacing 2 ${\AA}$. After the PLS analysis the best predicted CoMSIA model with hydrophobicity, hydrogen bond donor and acceptor property showed that a leave-one out(LOO) cross validated value $({r^2}_{cv})^$ and non-cross validated conventional value $({r^2}_{ncv})^$ are 0.543 and 0.938, respectively.

• 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.

• 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.

• 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).

• Journal of Applied Biological Chemistry
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• 제53권2호
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• pp.99-104
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• 2010

3차원적인 정량적 구조-활성상관(3D-QSAR: 비교분자 유사성지수분석(CoMSIA) 및 비교분자장분석(CoMFA)) 기법에 기초하여 4-Methyl-2H-benzopyran-2-one 유도체들(1-23)의 항산화활성에 관한 benzo 고리상 치환기($R_1-R_4$)들의 영향을 정량적으로 검토하였다. CoMSIA 모델은 CoMFA 모델보다 통계적으로 양호하였으며 최적화된 CoMSIA 2 모델의 예측성($q^2$=0.700)과 상관성($r^2$=0.979)이 가장 양호하였다. 항산화 활성에 관한 CoMSIA 2 모델의 기여비율(%)은 수소결합 주게장(HD) 43.5%, 정전기장(E) 41.8% 및 입체장(S) 14.7%로 정전기장과 H-결합 주게장이 항산화활성에 가장 큰 영향을 미치는 요소이었다. CoMSIA 등고도 분석결과, benzo 고리상에 양하전을 선호하며, 그리고 H-결합주게가 아닌 치환기($R_1-R_4$)들이 항산화활성을 증가시킬 것으로 예상되었다.

• 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.

• Applied Biological Chemistry
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• 제51권1호
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• pp.38-43
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• 2008

시들음병균(Fusarium oxysporum)의 살균활성에 관한 N-phenylbenzenesulfonamide 유도체들의 3차원적인 정량적 구조-활성관계(3D-QSARs)들을 비교 분자장 분석(CoMFA)과 비교분자 유사성 지수분석(CoMSIA) 방법으로 각각 검토하였다. 전반적으로 CoMFA 모델들이 CoMSIA 모델들 보다 좋은 통계값을 나타내었다. 그리고 최적의 CoMFA 2 모델($r^2\;_{cv.}=0.523$ 및 $r^2\;_{ncv.}=0.956$)의 정보에 따라 살균활성은 주로 정전기장에 의존적이었다. 또한 최적의 CoMFA 2 모델에 의한 등고도 분석결과로부터 N-phenyl 고리상 R4-치환기의 입체성과 양전하를 선호하는 성질이 시들음병균의 살균활성에 기여할 것으로 예상되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제13권6호
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• pp.511-516
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• 2009

A series of substituted 2-arylnaphthyridin-4-one analogues, which were previously synthesized in our laboratory, were evaluated for their in vitro cytotoxic activity against human lung cancer A549 and human renal cancer Caki-2 cells using MTT assay. Some compounds (11, 12, and 13) showed stronger cytotoxicity than colchicine against both tumor cell lines, and compound 13 exhibited the most potent activity with $IC_{50}$ values of 2.3 and $13.4\;{\mu}M$, respectively. Three-dimensional quantitative structure activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed. Predictive 3D-QSAR models were obtained with $q^2$ values of 0.869 and 0.872 and $r^2_{ncv}$ values of 0.983 and 0.993 for CoMFA and CoMSIA, respectively. These results demonstrate that CoMFA and CoMSIA models could be reliably used in the design of novel cytotoxic agents.