• Bulletin of the Korean Chemical Society
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• 제27권2호
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• pp.273-276
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• 2006

Three dimensional quantitative structure-activity relationship studies for a series of isatin derivatives as a nonpeptidyl caspase-3 enzyme inhibitor were investigated using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The first approach of non-peptidyl small molecules by 3D QSAR may be useful in guiding further development of potent caspase-3 inhibitors.

• 농약과학회지
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• 제2권2호
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• pp.16-21
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• 1998

비스 방향족 ${\alpha},{\beta}$-불포화 케톤 유도체의 헤테로 방향족고리($R_{1}$) 치환체중 치환 phenyl backbone($R_{2}$)들의 구조변환에 따른 벼도열병균(Pyricularia oryzae)과 토마토역병균(Phytophthora irifestans)에 대한 in vivo에서의 항균활성 관계(SAR)를 3-D QSAR 방법인 비교분자장 분석(CoMFA)으로 해석하였다. 두 식물병원균에 대한 항균활성을 설명하는 CoMFA결과는 2-D QSAR에서 검토된 결과와 유사한 경향이었으며 입체효과(Es)와 전자효과(${\sigma}$)로 설명할 수 있었다. 즉, 벼도열병균은 aryl group에 bulky한 치환기(Es>0)가 도입되어야 하며 ${\beta}$탄소원자의 양하전이 증가할수록 강한 항균활성을 나타낼것으로 기대되었다. 반면, 토마토역병균의 경우에는 aryl group에 체적이 작은 치환기가 도입될수록, 그리고 ${\beta}$ 탄소원자의 양하전이 감소할수록 강한 항균활성을 나타낼 것으로 기대 되었다. 또한, 입체효과와 전자효과를 등 고도로 나타낸 CoMFA결과가 기존의 2-D QSAR보다 항균활성에 미치는 화합물의 구조적 요인을 보다 구체적으로 제시할 수 있었다.

• 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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• 제4권2호
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• pp.99-102
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• 2011

Effect of protonation and deprotonation of ionization compounds is an important application in Comparative molecular field analysis (CoMFA). There are enough information's were reported about different CoMFA applications such as Series design and selection of training set, Geometries and optimizations of molecules, Effect of partial atomic charges, bioactive conformations and alignment, Interaction energy fields, Effects of different grid spacing etc. However limited information's are available about the ionization of compounds. This study aimed at the critical review of about the effects of protonation of ionizable molecules and its impact on the predictability of CoMFA models. We also discussed about previous implications and the things needed to be considered to come for a final conclusion about its impact on CoMFA predictability.

• 약학회지
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• 제54권4호
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• pp.288-294
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• 2010

Three dimensional quantitative-structure relationships (3D-QSARs) models between structures of phenoxy, phenylthio or benzyloxy substituted quinolone analogues and their antitrypanosomal activity against Chagas disease (Trypanosoma cruzi) were derived and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The optimized CoMFA 1 model ($q^2$=0.528 and $r^2$=0.964) showed the best statistical results. According to the optimized CoMFA 1 model, the antitrypanosomal activities were dependent on the steric (60.0%) and electrostatic (36.2%) factors of quinolone derivatives. From the contour maps, it is predicted that the activity will be increased when sterically favored groups were located in $R_4$ and $R_5$ position and sterically disfavored groups were located in $R_2$ position. Also, the positively charged groups on $R_2$ would be able to increase the antitrypanosomal activities.

• 통합자연과학논문집
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• 제4권3호
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• pp.216-221
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• 2011

c-Jun N-terminal kinase-3 (JNK-3) has been shown to mediate neuronal apoptosis and make the promising therapeutic target for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and other CNS disorders. In order to better understand the structural and chemical features of JNK-3, comparative molecular field analysis (CoMFA) was performed on a series of 3,5-disubstituted quinolines derivatives. The best predictions were obtained CoMFA model ($q^2$=0.707, $r^2$=0.972) and the statistical parameters from the generated 3D-QSAR models were indicated that the data are well fitted and have high predictive ability. The resulting contour map from 3D-QSAR models might be helpful to design novel and more potent JNK3 derivatives.

• 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.

• 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.249.2-250
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• 2003

3D-QSAR analyses by CoMFA and CoMSIA were conducted on a series of thiazole and triazole analogues with respect to their antifungal activities against Microsporum gypseum. A total of twenty analogues were used for the derivation of the 3D-QSAR models (training set). Thesuperposition of the compounds was performed by applying the FlexS with shape-based screening method. (omitted)

• 농약과학회지
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• 제14권4호
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• pp.319-325
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• 2010

두 점박이 응애(Tetranychus urticae)에 대한 N'-phenyl-N-methylformamidine 유도체(1-22)의 살충활성에 관한 치환기 ($R_1{\sim}R_4$)들의 영향을 이해하기 위하여 3차원적인 정량적 구조-활성관계(3D-QSAR) 모델인 비교분자장분석(CoMFA) 모델 및 비교분자 유사성지수분석(CoMSIA) 모델을 유도하고 정량적으로 검토하였다. 그 결과로부터 CoMFA 1 모델의 예측성 및 상관성($r^2{_{cv.}}=0.575$ 및 $r^2{_{ncv.}}=0.945$)이 가장 양호하였다. 또한, 순자혼합화 분석으로부터 CoMFA 1 및 CoMSIA 1 모델($d_q{^{2'}}/dr^2{_{yy}}=1.071{\sim}1.146$ 및 $q^2=0.545{\sim}0.626$)은 우연상관성에 저촉되지 않는 최적화 모델이었다. 최적화된 CoMFA 1 모델로 부터 두 점박이 응애에 대한 N'-phenyl-N-methylformamidine 유도제들의 저해활성에 관한 기여비율은 입체장 62.5%, 정전기장 28.9% 및 소수성장 8.6% 이었다. 그러므로 CoMFA 1 모델에 의한 살충활성은 입체장에 의존적이었다. 또한, 최적화 모델들의 등고도로부터 살충활성에 기여하는 구조적인 특징들은 새로운 살충제들을 설계하는데 적용할 수 있을 것으로 예상된다.

• 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.