• 대한화장품학회지
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• 제35권4호
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• pp.271-276
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• 2009

기질 화합물로써 일련의 4-($R_1$)-benzyl alcohol 및 4-($R_2$)-phenol 유도체들의 치환기($R_1$ 및 $R_2$)가 변화함에 따른 tyrosinase 활성저해에 관한 3차원적인 구조-활성 상관 (3D-QSARs) 모델을 유도하고 정량적으로 검토하였다. 그 결과, 입체장, 정전기장, 소수성장 및 수소결합 주게장의 조합조건에서 통계적으로 양호한 CoMSIA 2 모델(상관성; $r^2\;=\;0.858$ 및 예측성; $q^2\;=\;0.951$)을 유도하였다. 등고도 분석결과, 기질분자의 $R_2$-치환기는 입체적으로 작고 음전하를 띄며, 소수성이면서 수소결합 주게장을 선호하지 않는 치환기가, 그리고 $R_1$-치환기는 양전하를 띄며 수소결합 주게장을 선호하는 치환기가 tyrosinase의 저해활성이 증가 될 것으로 예상되었으며, 수소결합 받게장은 전혀 영향을 미치지 않았다.

• 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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• 제43권2호
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• pp.95-99
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• 2000

일련의 헤테로 고리 치환(X) chalcone 유도체들에 의한 farnesyl protein transferase(FPTase) 저해활성을 측정하여 분자내 styryl group의 치환기(Y) 변화에 따른 정량적인 구조와 FPTase 저해 활성과의 관계(QSARs)를 modified Free-Wilson(F-W)방법 및 Hansch 방법으로 분석 검토하였다. F-W 분석에 따르면 (X)-치환기는 FPTase 저해 활성에 기여하지 않았다 그러나 (Y)-치환기들은 ortho>meta>para 치환체의 순서로 ortho-치환체와 ${\alpha}$탄소의 알짜 전하$(C_{\alpha})$가 활성에 기여하였다. 모든 헤테로 고리 치환체에 대한 Hansch 분석에 의하면 전자 밀게(R<0)의 폭$(B_1)$이 작은 ortho-치환체로서 적정값, $(R)_{opt.}=-0.35$를 갖는 공명상수가 저해활성에 영향을 미친다는 사실을 알 수 있었다. 그리고 헤테로 치환체들 사이의 FPTase 저해활성은 모두 비례관계를 보임으로써 같은 경향으로 저해활성이 발현되었으며 비(H)치환체 45가 제일 높은 FPTase 저해활성$(pI_{50}=4.30)$을 보였다.

• Journal of Applied Biological Chemistry
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• 제50권2호
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• pp.52-57
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• 2007

Quantitative structure-activity relationships (QSARs) on the inhibition activities by oleanolic acid analogues (1-19) as a potent inhibitor against protein tyrosine phosphatase-1B were studied quantitatively using 2D-QSAR and HQSAR methodologies. The inhibition activity was dependent on the variations of $R_{4-}$substituent, and as shown in 2D-QSAR model ($r^2=0.928$), it has a tendency to increase as the negative Randic Indice (RI) goes up. The size of the molecular fragments used in HQSAR varied from five to eight. The fragment distinctions had the best statistic value, whose predictability is $q^2=0.785$ and correlation coefficient is $r^2=0.970$, on condition of connections. From the atomic contribution maps, the factor that contributes to the inhibition activities is the $C_{15}{\sim}C_{17}$ bond in the D ring. From the analysis result of these two the models, the structural distinctions and descriptors that contribute to the inhibition activities were obtained.

• 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.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.733-740
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• 2003

To find a new substance with superior melanogenesis inhibitory activity, the bioactivities of alkyl-3,4-dihydroxy-5-substituted benzoate (A) and N-alkyl-3,4-dihydroxy-5-substituted benzamide (B) derivatives as substrate of tyrosinase were measured in mouse melanoma cells. And the bioactivities analyzed using comparative molecular similarity indices analysis (CoMSIA). From the CoMSIA model, when cross-validation value (q$^2$) is 0.713 at four components, the pearson correlation coefficient ($r^2$) is 0.900. Unknown compounds were predicted, using QSAR analyzed results from the CoMSIA methods. Excellent agreement was obtained between the measured and the predicted bioactivities of unknown compounds. As the results of prediction from CoMSIA, we could conclude that the bioactivities were increased from pl$_{50}$=3.18-4.80 to above 5.17 by creation of 6-methylheptyl, n-pentylphenyl and 2-hydroxypentylphenyl group etc,.,.

• 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.

• Reproductive and Developmental Biology
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• 제33권3호
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• pp.119-123
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• 2009

The two dimensional quantitative structure-activity relationships (2D-QSARs) models concerning the binding affinity constants ($p[Od.]_{50}$) between 2-cyclohexyltetrahydropyrane and 2-cyclohexyltetrahydrofurane analogues as substrates, and bovine odorant binding protein (bOBP) as receptor were derived by multiple regression analyses method and discussed. The statistical quality of the optimized 2D-QSAR model (5) was good (r=0.907). From the model, the binding affinity constants ($p[Od.]_{50}$) were dependent upon the optimal value ($(TL)_{opt.}$=2.737) of total lipole (TL) of substrate molecules. Based on these findings, the high active compounds predicted by optimized 2D-QSAR model (5) were 2-(dimethylcyclohexyl)tetrahydropyrane molecule and their isomer molecules. The binding affinity constants regarding bOBP of the tetrahydrofuryl-2-yl family compounds were dependent upon the hydrophobicity (logP) of whole substrate molecules. In any case of porcine odorant-binding proteins (pOBP), the constants were dependent upon the hydrophobicity (${\pi}x={\log}P_X-{\log}P_H$) of substituents (R) in substrate molecules. Also, from the optimal values of hydrophobic constant, the hydrophobicity for bOBP influenced ca. twice time bigger (bOBP>pOBP) than that for pOBP.

• Bulletin of the Korean Chemical Society
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• 제31권5호
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• pp.1355-1360
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• 2010

In order to search new inhibitors against farnesyl protein transferase (FPTase), a series of 2,3-bis-benzylidenesuccinaldehyde derivatives (1-29) were synthesized and their inhibition activities ($pI_{50}$) against FPTase were measured. From based on the reported results that the inhibitory activities of dimers 2,3-bis-benzylidenesuccinaldehydes were higher than those of monomers cinnamaldehydes, 3D-QSARs on FPTase inhibitory activities of the dimers (1-29) were studied quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The statistical qualities of the optimized CoMFA model II ($r^2{_{cv.}}$= 0.693 and $r^2{_{ncv.}}$= 0.974) was higher than those of the CoMSIA model II ($r^2{_{cv.}}$ = 0.484 and $r^2{_{ncv.}}$ = 0.928). The dependence of CoMFA models on chance correlations was evaluated with progressive scrambling analyses. And the inhibitory activity exhibited a strong correlation with steric factors of the substrate molecules. Therefore, from the results of graphical analyses on the contour maps and of predicted higher inhibitory active compounds, it is suggested that the structural distinctions and descriptors that contribute to inhibitory activities ($pI_{50}$) against FPTase will be able to applied new inhibitor design.

• Bulletin of the Korean Chemical Society
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• 제34권7호
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• pp.1972-1984
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• 2013

Microtubules play an important role in intracellular transport, mobility, and particularly mitosis. Paclitaxel (Taxol$^{TM}$) and paclitaxel-like compounds have been shown to be anti-tumor agents useful for various human tumors. Paclitaxel-like compounds operate by stabilizing microtubules through interface binding at the interface between two ${\beta}$-tubulin monomers in adjacent protofilaments. In this paper we present the elucidation of the structural features of paclitaxel and paclitaxel-like compounds (e.g., epothilones) with microtubule stabilizing activities, and relate their activities to spatial and chemical features of the molecules. CATALYST program was used to generate three-dimensional quantitative structure activity relationships (3D-QSARs) resulting in 3D pharmacophore models of epothilone- and paclitaxel-derivatives. Pharmacophore models were generated from diverse conformers of these compounds resulting in a high correlation between experimental and predicted biological activities (r = 0.83 and 0.91 for epothilone and paclitaxel derivatives, respectively). On the basis of biological activities of the training sets, five- and four-feature pharmacophore hypotheses were generated in the epothilone and paclitaxel series. The validation of generated hypotheses was achieved by using twelve epothilones and ten paclitaxels, respectively, which are not in the training sets. The clustering (grouping) and merging techniques were used in order to supplement spatial restrictions of each of hypothesis and to develop more comprehensive models. This approach may be of use in developing novel inhibitor candidates as well as contributing a better understanding of structural characters of many compounds useful as anticancer agents targeting microtubules.