• Bulletin of the Korean Chemical Society
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• v.31 no.11
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• pp.3297-3300
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• 2010

In this study, the 3D-QSARs (three-dimensional quantitative structure-activity relationships: CoMFA and CoMSIA) between structural changes of N-phenyl-O-phenylthionocarbamate analogues (1-30) and their fungicidal activities against the capsicum phytophthora (Phyophthora capsici) fungi were analyzed, then considered quantitatively in terms of minimum structural requirements for fungicidal evaluation. The statistical qualities ($r^2_{cv.}$ = 0.510 and $r^2_{ncv.}$ = 0.948) of the optimal CoMFA 1 model are improved over the other models in the conditions of field combinations, and the two alignments. In the optimal CoMFA 1 model, relative contribution percentages of the CoMFA field were: steric field, 52.3%; electrostatic field, 37.8%; hydrophobic field, 9.9%. Results were similar for the CoMFA 2 model. Therefore, the steric field of the analogues had the highest contribution ratio for fungicidal activity. Specifically, with the contour map of steric fields, the fungicidal activity increased when bulky steric Y-substituents were introduced to the meta-position on the N-phenyl ring and small steric Y-subsituents were introduced to its para-position.

• The Korean Journal of Pesticide Science
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• v.11 no.3
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• pp.138-143
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• 2007

The relationships between three dimensional quantitative structure and activity relationships (3D-QSARs) for the selective fungicidal function between N-phenyl substituents of N-phenyl-O-phenyl-thionocarbamate derivatives analogues and their the fungicidal activities against resistant (RBC) and sensitive (SBC) gray mold (Botrytis cinerea) were studied quantitatively using CoMFA and CoMSIA methods. The statistical values of optimized CoMSIA (M7) model were better ($r^2$ & $q^2=CoMSIA{\gg}CoMFA$) than that of CoMFA (M5) model. And the factor influencing of the selective between the fungicidal activity against RBC and SBC was dependent on electrostatic field of CoMFA (M5) model. Therefore, it is predicted that, from the CoMSIA contour maps of CoMSIA (M7) model, the selectivity will be improved by the H-bond donor that is with negatively charged favored group at meta-position on the N-phenyl ring.

• Korean Journal of Agricultural Science
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• v.34 no.2
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• pp.171-179
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• 2007

The new insecticidal active molecules from the based on the holographic quantitative structure-activity relationships (HQSAR) between a series of $1-(R_1)-2-(n-octyl)-3-(R_2)$, $3-(R_3)-pseudothiourea$ derivatives and their insecticidal activities against Diamond-back moth (Plutella Xylostella Linnaeus) were designed and discussed quantitatively. The most active molecule from the based graphical analyses of atomic contribution maps with the optimized HQSAR C-1 model ($q^2=0.764$ & $r^2{ncv}=0.942$) was 1-(n-butyl)-2-(t-butyl)-3,3-diisopropylpseudothiourea (P1: $pI_{50}=5.30$, $IC_{50}=1.397ppm$). Therefore, it is suggested that the new designed molecule would increased the activity as much as 23.5 times as compared to X=n-octyl substituent 17($pI_{50}=4.00$, $IC_{50}=32.86ppm$) which was the highest active molecule in training set compounds.

• Bulletin of the Korean Chemical Society
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• v.29 no.3
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• pp.656-662
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• 2008

Antagonists of the d -opioid receptor are effective in overcoming resistance against analgesic drugs such as morphine. To identify novel antagonists of the d -opioid receptor that display high potency and low resistance, we performed 3D-QSAR analysis using chemical feature-based pharmacophore models. Chemical features for d -opioid receptor antagonists were generated using quantitative (Catalyst/HypoGen) and qualitative (Catalyst/HipHop) approaches. For HypoGen analysis, we collected 16 peptide and 16 non-peptide antagonists as the training set. The best-fit pharmacophore hypotheses of the two antagonist models comprised identical features, including a hydrophobic aromatic (HAR), a hydrophobic (HY), and a positive ionizable (PI) function. The training set of the HipHop model was constructed with three launched opioid drugs. The best hypothesis from HipHop included four features: an HAR, an HY, a hydrogen bond donor (HBD), and a PI function. Based on these results, we confirm that HY, HAR and PI features are essential for effective antagonism of the d -opioid receptor, and determine the appropriate pharmacophore to design such antagonists.

• Journal of Integrative Natural Science
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• v.4 no.2
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• pp.91-98
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• 2011

Quantitative structure-activity relationships (QSAR) have been applied for two decades in the development of relationships between physicochemical properties of chemical substances and their biological activities to obtain a reliable statistical model for prediction of the activities of new chemical entities. The fundamental principle underlying the QSAR is that the structural difference is responsible for the variations in biological activities of the compounds. In this work, we developed 3D-QSAR model for a series of 5-Lipoxygenase inhibitors, utilizing comparative molecular field analysis (CoMFA) and Topomer CoMFA methodologies. Our developed models addressed superiority of Topomer CoMFA over CoMFA. The CoMFA model was obtained with $q^2$=0.593, $r^2$=0.939, $Q^2$=0.334 with 6 optimum number of components (ONC). Higher statistical results were obtained with the Topomer CoMFA model ($q^2$=0.819, $r^2$=0.947, ONC=5). Further robustness of developed models was checked with the ANOVA test and it shows F=113 for CoMFA and F=162.4 for Topomer CoMFA model. Contour map analysis indicated that the more requirement of electrostatic parameter for improved potency.

• Environmental Analysis Health and Toxicology
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• v.16 no.3
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• pp.115-120
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• 2001

The predictive screening of various molecular descriptors for predicting cyclooxygenase inhibitor, lipooxygenase inhibitor, leucotriene synthesis inhibitor, leucotriene antagonist activities of Stilbene moieties have been investigated for the application of quantitative structure-activity relationships (QSAR). The biological activities for 36 compounds were computed by the PASS program and molecular descriptors are cited from literatures or calculated, to investigate feasibility of screening relevant descriptors and of their applications among biological endpoints. Fairly good correlations varying from 0.7828 to 0.9032 were obtained using 12 descriptors with 29 Stilbene derivatives and 5 diazo-compounds. Our studies reveal that LogKow, electron density(X), electron density (Y),4th-order valence connectivity and water solubility can be usefully employed to predict biological activities of stilbene derivatives with simple regression models.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.84-85
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• 2003

Benzoyl peroxide is a High Production Volume Chemical, which is produced about 1,375 tons/year in Korea as of 2001 survey. The substance is mainly used as initiators in polymerization, catalysts in the plastics industry, bleaching agents for flour and medication for acne vulgaris. In this study, Quantitative Structure-Activity Relationships (QSAR) is used for getting information on the physical-chemical properties of this chemical. (omitted)

• Environmental Analysis Health and Toxicology
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• v.18 no.4
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.517-523
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• 2013

Naphthyridine compounds are important, because they exhibit various biological activities including anticancer, antimicrobial, and anti-inflammatory activity. Some naphthyridines have antimitotic effects or demonstrate anticancer activity by inhibiting topoisomerase II. These compounds have been investigated as potential anticancer agents, and several compounds are now part of clinical trials. A series of naphthyridine derivatives were evaluated for their in vitro cytotoxic activities against human cervical cancer (HeLa), leukemia (HL-60), and prostate cancer (PC-3) cell lines using an MTT assay. Some compounds (14, 15, and 16) were more potent than colchicine against all three human cancer cell lines and compound (16) demonstrated potency with $IC_{50}$ values of 0.7, 0.1, and $5.1{\mu}M$, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used for quantitative structure-activity relationship (QSAR) molecular modeling of these compounds. We obtained accurate and predictive three-dimensional QSAR (3D-QSAR) models as indicated by the high PLS parameters of the HeLa ($q^2$, 0.857; $r^2$, 0.984; $r^2\;_{pred}$, 0.966), HL-60 ($q^2$, 0.777; $q^2$, 0.937; $r^2\;_{pred}$, 0.913), and PC-3 ($q^2$, 0.702; $q^2$, 0.983; $r^2\;_{pred}$, 0.974) cell lines. The 3D-QSAR contour maps suggested that the C-1 NH and C-4 carbonyl group of the naphthyridine ring and the C-2 naphthyl ring were important for cytotoxicity in all three human cancer cell lines.

• Applied Biological Chemistry
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• v.47 no.3
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• pp.351-356
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• 2004

Holographic quantitative structure activity relationships (HQSAR) as 2D QSAR between the herbicidal activities against root and shoot of rice plant (Orysa sativa L.) and barnyardgrass (Echinochloa crus-galli), and structures of A=3,4,5,6-tetra-hydrophthalimino, B = 3-chloro-4,5,6,7-tetrahydro-2H-indazolyl and C = 3,4-dimethylmaleimino substituents in 1-(5-methyl-3-phenylisoxazolin-5-yl)methoxy-2-chloro-4-fluorobenzene derivatives were studied and discussed. The statistical results of four HQSAR models for the herbicidal activities against root and shoot of the two plants showed the best predictability of the herbicidal activities based on the cross-validated $r^2\;_{cv}\;(q^2=\;0.760{\sim}0.924)$, non cross-validated conventional coefficient $(r^2\;_{ncv}\;=\;0.868{\sim}0.970)$ and PRESS values $(0.123{\sim}0.261)$. The results indicated that the qualities of HQSAR models for barnyardgrass were slightly higher than that of rice plant. And also, the predictability of HQSAR models were higher $(q^2\;=\;HQSAR\;>\;CoMFA)$ than CoMFA but the conventional coefficients of HQSAR models lower $(r^2\;=\;HQSAR\;<\;CoMFA)$ than CoMFA. Moreover, from the contribution maps, it was founded that the selectivity between the two plants depends upon the 2-fluoro-4-chloro-5-alkoxyanilino and $R_3$ substituent on the C-phenyl ring. These features suggest where to modify a molecular structure in order to improve its selective of herbicidal activities against barnyardgrass.