• 농약과학회지
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• 제7권1호
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• pp.1-11
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• 2003

새로운 농약을 탐색하고 개발하는데 있어서 고효율 유기함성 (HTOS) 기술과 고효율 검색 (HTS) 기술 등의 발전과 더불어 컴퓨터 화학을 이용한 분자설계 (CAMD) 방법으로 보편화되고 있는 비교 분자장 분석(CoMFA)과 비교 분자 유사성 지수분석(CoMSIA) 등, 3D QSAR 기법들을 위시하여 분자 홀로그램 구조 - 활성관계 (HQSAR) 분석방법 등, QSAR 기법들을 요약하고 그 활용 사례들을 간략하게 소개하였다.

• Bulletin of the Korean Chemical Society
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• 제32권7호
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• pp.2433-2442
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• 2011

The three dimensional quantitative structure activity relationship (3D QSAR) models were developed using Comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and docking studies. The fit of Quinazolinone antifolates inside the active site of modeled bovine dihydrofolate reductase (DHFR) was assessed. Both ligand based (LB) and receptor based (RB) QSAR models were generated, these models showed good internal and external statistical reliability that is evident from the $q^2_{loo}$, $r^2_{ncv}$ and $r^2_{pred}$. The identified key features enabled us to design new Quinazolinone analogues as DHFR inhibitors. This study is a building bridge between docking studies of homology modeled bovine DHFR protein as well as ligand and target based 3D QSAR techniques of CoMFA and CoMSIA approaches.

• Bulletin of the Korean Chemical Society
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• 제25권10호
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• pp.1513-1520
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• 2004

We investigate a series of synthesized ${\beta}$-methoxyacrylate analogues for their 3D QSAR & HQSAR against Magnaporthe grisea (Rice Blast Disease). We perform the three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) studies, using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) procedure. In addition, we carry out a two-dimensional Quantitative Structure-Activity Relationship (2D-QSAR) study, using the Hologram QSAR (HQSAR). We perform these studies, using 53 compounds as a training set and 10 compounds as a test set. The predictive QSAR models have conventional $r^2$ values of 0.955 at CoMFA, 0.917 at CoMSIA, and 0.910 at HQSAR respectively; similarly, we obtain cross-validated coefficient $q^2$ values of 0.822 at CoMFA, 0.763 at CoMSIA, and 0.816 at HQSAR, respectively. From these studies, the CoMFA model performs better than the CoMSIA model.

• Archives of Pharmacal Research
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• 제23권4호
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• pp.324-328
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• 2000

Three dimensional QSAR studies for antihistamine and antibradykinin effects of new piperazine derivatives were conducted using the comparative molecular field analysis. Electrostatic and steric factors, but not hydrophobic factor, of the synthesized compounds were correlated with the antagonistic effect.

• 한국환경보건학회지
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• 제38권6호
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• pp.550-560
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• 2012

Objectives: QSAR methodology was applied to explain two different sets of acceptable daily intake (ADI) data of 74 pesticides proposed by both the USEPA and WHO in terms of setting guidelines for food and drinking water. Methods: A subset of calculated descriptors was selected from Dragon$^{(R)}$ software. QSARs were then developed utilizing a statistical technique, genetic algorithm-multiple linear regression (GA-MLR). The differences in each specific model in the prediction of the ADI of the pesticides were discussed. Results: The stepwise multiple linear regression analysis resulted in a statistically significant QSAR model with five descriptors. Resultant QSAR models were robust, showing good utility across multiple classes of pesticide compounds. The applicability domain was also defined. The proposed models were robust and satisfactory. Conclusions: The QSAR model could be a feasible and effective tool for predicting ADI and for the comparison of logADIEPA to logADIWHO. The statistical results agree with the fact that USEPA focuses on more subtle endpoints than does WHO.

• Bulletin of the Korean Chemical Society
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• 제29권3호
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• pp.647-655
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• 2008

Microsomal prostaglandin E2 synthase (mPGES-1) is a potent target for pain and inflammation. Various QSAR (quantitative structure activity relationship) analyses used to understand the factors affecting inhibitory potency for a series of MK886 analogues. We derived four QSAR models utilizing various quantum mechanical (QM) descriptors. These QM models indicate that steric, electrostatic and hydrophobic interaction can be important factors. Common pharmacophore hypotheses (CPHs) also have studied. The QSAR model derived by best-fitted CPHs considering hydrophobic, negative group and ring effect gave a reasonable result (q2 = 0.77, r2 = 0.97 and Rtestset = 0.90). The pharmacophore-derived molecular alignment subsequently used for 3D-QSAR. The CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Indices Analysis) techniques employed on same series of mPGES-1 inhibitors which gives a statistically reasonable result (CoMFA; q2 = 0.90, r2 = 0.99. CoMSIA; q2 = 0.93, r2 = 1.00). All modeling results (QM-based QSAR, pharmacophore modeling and 3D-QSAR) imply steric, electrostatic and hydrophobic contribution to the inhibitory activity. CoMFA and CoMSIA models suggest the introduction of bulky group around ring B may enhance the inhibitory activity.

• 농약과학회지
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• 제11권2호
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• pp.72-81
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• 2007

일련의 새로운 O,O-dialkyl-1-phenoxyacetoxy-1-methylphosphonate (S) 유도체들의 반응성과 치환기가 변화함에 따른 오이(Cucumus Sativa)씨에 대한 발아전 제초활성과의 관계를 2D-QSAR 및 HQSAR 방법으로 검토하였다. 통계적으로 HQSAR 모델이 2D-QSAR 모델보다 양호하였으며 기질분자(S)와 PDH 효소중 $BH^+$ 이온(I) 사이의 경계분자궤도(FMO) 상호작용은 친전자성 반응이 우세하였다. 치환기의 효과로부터 기질분자 (S)내 $R_2$-치환기는 carbonyl 산소원자에 대한 친전자성 반응을, 그리고 phenyl 고리상 X,Y-치환기는 carbonyl 탄소원자에 대한 친핵성 반응에 기여하였으며 $R_2$-치환기보다 X,Y-치환기의 영향이 더 컸다. 2D-QSAR모델 (I 및 II)과 HQSAR 모델의 기여도로부터 X,Y-치환기의 길이가 길수록 제초활성이 증가하는 경향이었으며 적정한 ${\epsilon}LUMO$ 에너지($({\epsilon}LUMO)_{opt.}$=-0.479 e.v.)가 제초활성에 중요한 요소이었다. 그러므로 PDH 효소의 저해활성으로 인한 제초활성은 친핵성반응으로 진행될 것으로 예상되었다. 2D-QSAR 및 HQSAR 두 모델로부터 제초활성에 기여하는 기질분자(S)의 구조 특이성과 요소들을 새로운 제초제 설계에 적용할 수 있음을 시사하였다.

• 농약과학회지
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• 제12권1호
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• pp.9-17
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• 2008

일련의 새로운 cyclohexanone 유도체(5-benzofuryl-2-[1-(alkoxyimino)alkyl]-3-hy-droxycyclohex-2-en-1-ones)와 벼(Oryza sativa L.) 및 돌피(Echinochloa crus-galli)에 대한 제초활성과의 정량적인 구조-활성관계(QSARs)를 2D-QSAR 및 HQSAR 방법으로 검토하였다. 일반적으로 HQSAR 모델이 2D-QSAR 모델보다 예측성과 적합성이 좋았다. 2D-QSAR II 모델로부터 돌피의 제초활성은 분자의 Balaban 지수(BI)와 $R_1$ 및 $R_3$-기의 소수성에 의존적이었다. 또한, HQSAR IV 모델에 따라 $R_3=ethyl$ 기가 벼의 제초활성에 기여하는 반면에 5-(cyclohex-3-enyl)-2,3-dihydrobenzofuran 고리 부분은 두 초종의 제초활성에 기여하지 않았다.

• Environmental Analysis Health and Toxicology
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• 제18권4호
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• pp.271-276
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• 2003

The purpose of the present study was to perform experiments of cytotoxicity using HeLa cell and to evaluate the possibility that QSAR is applicable to the cytotoxicity of alkylphenols. Higher toxicities were found in four alkylphenols in the following order: 4-n-Nonylphenol) 4-tert-Octylphenol) 4-n-Octylphenol > 4-n Heptylpheonl. Whereas other alkylphenols were apparently less toxic. By using Percent Hydrophilic Surface Area (PHSA) quantitative structure-activity relationships (QSARs) models were developed: Cytotoxicity (%) = 90.14089-4.72224 PHSA ($R^2$=0.2046, $\alpha$=0.0265). It is concluded that some of the obtained data are useful to determine whether QSAR methods can be of general use in predicting that until further work is undertaken to develop QSARs for a much wider range of homologous series of alkylphenol compounds.

• 대한화학회지
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• 제59권6호
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• pp.483-487
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• 2015

The different calculated quantum chemical descriptors by DFT method were used for prediction of some sulphanilamide Schiff bases inhibitor activity as a binding constant (log K). Multiple linear regression (MLR) and artificial neural network (ANN) were employed for developing the useful quantitative structure activity relationship (QSAR) model. The obtained results presented superiority of ANN model over the MLR one. The offering QSAR model is very easy to computation and Physico-Chemically interpretable. Sensitivity analysis was used to determine the relative importance of each descriptor in ANN model. The order of importance of each descriptor according to this analysis is: molecular volume, molecular weight and dipole moment, respectively. These descriptors appear good information related to different structure of sulphanilamide Schiff bases can participate in their inhibitor activity.