• Applied Biological Chemistry
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• v.51 no.2
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• pp.119-123
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• 2008

3D-QSARs (3 dimensional quantitative structrue-activity relationships) on the inhibition activities of 3-substituted-5,5'-diphenylimidazolidine-2,4-dione derivatives (1-22) against FAAH (fatty acid amide hydrolase) were studied quantitatively using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indice analysis) methods. The statistical results of the CoMFA 1A and CoMSIA 2F model are better predictability and fitness. And also, the designed X=I, Y=$N_{2}^{+}$-substituent (P1: $Pred.pI_{50}$=6.55), according to the contour maps with information of the two models, showed the most inhibition activity against FAAH.

• Applied Biological Chemistry
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• v.51 no.3
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• pp.171-176
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• 2008

The comparative molecular similarity indices analysis (CoMSIA) models between 3${\beta}$-Hydroxy-12-oleanen-28-oic acid (1-30) analogues as substrate molecule and their inhibitory activities ($pI_{50}$) against protein tyrosine phosphatase (PTP)-1B were derived and discussed quantitatively. Listing in order, the CoMFA>CoMSIA${\geq}$HQSAR>2D-QSAR model, these QSAR models had the better statistical values. The optimized CoMSIA F1 model at grid 3.0${\AA}$ had the best predictability and fitness ($q^2$=0.754 and $r^2$=0.976) by field fit alignment. The order of contribution ratio (%) of CoMSIA fields concerning the inhibitory activities was a H-bond acceptor (48.9%), steric field (25.8%) and hydrophobic field (25.4%), respectively. Therefore, the inhibitory activities of substrate molecules against PTP-1B were dependent upon H-bond acceptor field (A) of $R_4$-group. From the analytical results of CoMSIA contour maps, oleanolic acid derivatives will have better inhibition activities if $R_1$ group has H-bond acceptor disfavor, $R_3$group has steric disfavor and $R_4$ group has steric, hydrophobic, H-bond favor.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.441-447
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• 2010

B13, a ceramide analogue, is a ceramidase inhibitor and induces apoptosis to give potent anticancer activity. A series of thiourea B13 analogues was evaluated for their in vitro cytotoxic activities against human renal cancer Caki-2 and leukemic cancer HL-60 in the MTT assay. Some compounds (12, 15, and 16) showed stronger cytotoxicity than B13 and C6-ceramide against both tumor cell lines, and compound (12) gave the most potent activity with $IC_{50}$ values of 36 and $9\;{\mu}M$, respectively. Molecular modeling of thiourea B13 analogues was carried out by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). We obtained highly reliable and predictive CoMSIA models with cross-validated $q^2$ values of 0.707 and 0.753 and CoMSIA contour maps to show the structural requirements for potent activity. These data suggest that the amide group of B13 could be replaced by thiourea, that the stereochemistry of 1,3-propandiol may not be essential for activity and that long alkyl chains increase cytotoxicity.

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.2065-2071
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• 2014

${\beta}$-Secretase (beta-amyloid converting enzyme 1 [BACE1]) is involved in the first and rate-limiting step of ${\beta}$-amyloid ($A{\beta}$) peptides production, which leads to the pathogenesis of Alzheimer's disease(AD). Therefore, inhibition of BACE1 activity has become an efficient approach for the treatment of AD. Ligand-based and docking-based 3D-quantitative structure-activity relationship (3D-QSAR) studies of acyl guanidine analogues were performed with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to obtain insights for designing novel potent BACE1 inhibitors. We obtained highly reliable and predictive CoMSIA models with a cross-validated $q^2$ value of 0.725 and a predictive coefficient $r{^2}_{pred}$ value of 0.956. CoMSIA contour maps showed the structural requirements for potent activity. 3D-QSAR analysis suggested that an acyl guanidine and an amide group in the $R_6$ substituent would be important moieties for potent activity. Moreover, the introduction of small hydrophobic groups in the phenyl ring and hydrogen bond donor groups in 3,5-dichlorophenyl ring could increase biological activity.

• The Korean Journal of Pesticide Science
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• v.12 no.2
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• pp.111-117
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• 2008

The comparative molecular field analysis (CoMFA) for the fungicidal activity with N-phenylbenzenesulfonamide analogues (1-45) against gray mold (Botriyts cinerea) were studied quantitatively. The statistical values of CoMFA models had much better predictability and fitness than those of comparative molecular similarity indices analysis (CoMSIA) models. The statistical values of the optimized CoMFA I model were predictablity, $r^2_{cv.}(or\;q^2)=0.457$ and correlation coefficient, $r^2_{ncv.}=0.959$, and their fungicidal activity was dependent on the steric field (52%) and electrostatic field (35.6%) of the substrate molecules. And also, it was found that the optimized CoMFA I model with the sensitivity to perturbation ($d_q^{2'}/dr^2_{yy'}=0.898$) and prediction ($q^2=0.346$ & SDEP=0.614) produced by a progressive scrambling analysis was not dependent on chance correlation. From the results of graphical analyses on the contour maps with the optimized CoMFA I model, it is expected that the $R_3$ and $R_4$-substituents on the N-phenyl ring as steric favor group and para-substituents ($R_1$) on the S-phenyl ring as steric disfavor group will contribute to the fungicidal activity. Therefore, the optimized CoMFA I model should be applicable to the prediction of the fungicidal activities against gray mold.

• Bulletin of the Korean Chemical Society
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• v.30 no.3
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• pp.613-617
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• 2009

3D-QSARs for the inhibition activities against protox by herbicidal 2-N-phenylisoindolin-1-one derivatives were studied quantitatively using CoMFA and CoMSIA methods. The result of the statistical quality of optimized CoMSIA model 2 ($FF:\;{r^2}_{cv.};\;0.973\;&\;{r^2}_{ncv.};\;0.612$) was higher than that of CoMFA model 1 ($AF:\;{r^2}_{cv.};\;0.414\;&\;{r^2}_{ncv.};\;0.909$). Also, the relative contribution of the optimized CoMSIA model 2 showed the steric (24.6%), electrostatic (31.0%), hydrophobic (ClogP, 23.4%) and H-bond acceptor field (21.0%), respectively. From the results of the contour maps, the protox inhibition activities are expected to increase when steric favor and H-bond acceptor favor groups are substituted on $R_2$ position and positive favor group are substituted on $C_2,\;C_3,\;and\;C_5$ atom in phenyl ring of $R_2$ position. And the inhibition activities are expected to increase when hydrophobic favor group is substituted on $C_1,\;C_3$ atom in phenyl ring of $R_2$ position and $C_1$ atom of $R_2$ position and hydrophilic favor groups are substituted on $C_4$ atom in phenyl ring of $R_1$ position and the terminal group of $R_1$ position.

• Bulletin of the Korean Chemical Society
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• v.31 no.5
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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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• v.33 no.1
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• pp.305-308
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• 2012

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.65.2-65.2
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• 2003

88 selective COX-2 inhibitors belonging to three chemical classes (triaryl rings, diaryl cycloalkanopyrazoles, and diphenyl hydrazides) were studied using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Partial least squares analysis produced statistically significant models with q values of 0.84 and 0.79 for CoMFA and CoMSIA, respectively. The key spatial properties were detected by careful analysis of the isocontour maps. The binding energies calculated from flexible docking correlated with inhibitory activities by the least-squares fit method. (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.247.2-248
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• 2003

The three-dimensional quantitative structure-activity relationship (3D-QSAR) approach using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) was applied to 62 derivatives known as COX-2 selective inhibitors. Partial least square (PLS) analyses produced good predicted models with q2 value of 0.803 (s=0.285, F=215.401, r2=0.951) and 0.769 (s=0.192, F=245.364, r2=0.980) for CoMFA and CoMSIA, respectively. (omitted)