• Proceedings of the PSK Conference
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• 2003.04a
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• pp.250.1-250.1
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• 2003

In this work, we have conducted 3D-QSAR studies on a series of acanthonic acid derivatives that act as COX-2 inhibitors, using two different methods: comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). CoMFA and CoMSIA analysis of twenty five pimarane analogues produced good models with high predictive abilities. (omitted)

• 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.

• Bulletin of the Korean Chemical Society
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• v.32 no.5
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• pp.1604-1612
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• 2011

We developed three-dimensional quantitative structure activity relationship (3D-QASR) models for 17 adamantyl derivatives as P-glycoprotein (P-gp) inhibitors. Eighteen different partial charge calculation methods were tested to check the feasibility of the 3D-QSAR models. Best predictive comparative molecular field analysis (CoMFA) model was obtained with the Austin Model 1-Bond Charge Correction (AM1-BCC) atomic charge. The 3D-QSAR models were derived with CoMFA and comparative molecular similarity indices analysis (CoMSIA). The final CoMFA model ($q^2$ = 0.764, $r^2$ = 0.988) was calculated with an AM1-BCC charge and electrostatic parameter, whereas the CoMSIA model ($q^2$ = 0.655, $r^2$ = 0.964) was derived with an AM1-BCC charge and combined steric, electrostatic, hydrophobic and HB-acceptor parameters. Leave-five-out (LFO) cross-validation was also performed, which yielded good correlation coefficient for both CoMFA (0.801) and CoMSIA (0.656) models. Robustness of the developed models was checked further with 1000 run bootstrapping analyses, which gave an acceptable correlation coefficient for CoMFA (BS-$r^2$ = 0.997, BS-SD = 0.003) and CoMSIA (BS-$r^2$ = 0.996, BS-SD = 0.018).

• Journal of the Korean Ceramic Society
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• v.42 no.6 s.277
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• pp.391-398
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• 2005

It is known that $BaMgAl_{10}O_{17}:Eu^{2+}(BAM)$ phosphors currently used have a serious thermal degradation problem. We screened $SrO-B_2O_3-P_2O_5$ system by a solution combinatorial chemistry technique in an attempt to search for a thermally stable blue phosphor for PDPs. A Quantitative Structure Activity Relationship (QSAR) was also obtained using an artificial neural network trained by the result fiom the combinatorial screening. As a result, we proposed a promising composition range in the $SrO-B_2O_3-P_2O_5$ ternary library. These compositions crystallized into a single major phase, $Sr_6BP_5O_{20}:Eu^{2+}$. The structure of $Sr_6BP_5O_{20}:Eu^{2+}$ was clearly determined by ab initio calculation. The luminescent efficiency of $Sr_6BP_5O_{20}:Eu^{2+}$ was 2.8 times of BAM at Vacuum Ultra Violet (VUV) excitation. The thermal stability was also good but the CIE color chromaticity was slightly poor.

• Microbiology and Biotechnology Letters
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• v.27 no.1
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• pp.54-61
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• 1999

Measurement of inhibition of bioluminescence in Photobacterium phosphoreum has been porposed as a sensitive and rapid procedure to monitor toxic substances. However, at first, $EC_{50}$ which shows degree of toxicity to each toxic substances must be calculated. QSAR (Quantitative Structure Activity Relationship) model can be used to estimate $EC_{50}$ to save time and endeavor. Moderately high correlation coefficients ($r^2{\geq}$ 0.97) were calculated from the linear correlation between $EC_{50}$ and molecular connectivity indices of CAHs (chlorinated aliphatic hydrocarbons)such as $^0X$, $^0X^V$, $^1X$, $^2X$ and $^3X^v_c$ and quadratic correlation between $EC_{50}$ and $^0X$, $^0X^V$, $^2X^V$, $^3X_c$, $^3X^V_c$ and P. It shows that the molecular connection indices in carbon structure is contributed to biological characters with linear relation and that in the other one with quadratic relation. The $EC_{50}$ of chlorophenol derivatives had quadratic relation with the value of octanol/water prtition coefficients ($r^2$=0.99) and linear and quadratic relation with the number of chlorine compound (($r^2{\geq}$0.94). This confirms the already known trend of increasing toxicity with increasing ability of a compound to diffuse through cell membrane and number of chlorine substitution.

• Archives of Pharmacal Research
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• v.13 no.1
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• pp.82-96
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• 1990

Ten (E)-and (Z)-isomers of 2-phenylcyclopropylamine (PCA), 1-Me PCA, 2-Me-PCA, N-Me-PCA, and N, N-diMe PCA and fifteen o-. m-, p- isomers of (E) PCA with substituents of Me, Cl, F, OMe, OH were synthesized in this laboratory and tested for the inhibition of rat brain mitochondrial MAO-A and MAO-B. The effects of substituents, their positions, and stereochemistry on the inhibition were assessed for the compounds with substituents at cyclopropyl and amino groups and QSAR analyses were performed using the potency data of ring-substituted compounds. The best correlated QSAR equations are as follows : pI$_{50}$ = 0.804 $\pi^2$-0.834 Blo-1.069 Blm + 0.334 Lp-1.709 HDp +7.897 (r = 0.945, s =0.211, F = 16.691, p = 0.000) for the inhibition of MAO-A;PI$_{50}$= 1.815$\pi$-0.825 $\pi^2$-1.203R + 0.900 Es$^2$ + 0.869 Es$^3$ + 0.796 Es$^4$-0.992 HDp + 0.562 HAo + 3.893 (r = 0.982, s =0.178, F = 23.351, p = 0.000) for the inhibition of MAO-B. Based on the potency difference between stereoisomers of cyclopropylamine-modified compounds and an QSAR cavity near para position, two hydrophobic carities interacting with Me group, a hydrophobic site near para position, and an amino group binding site and that in addition to the same two hydrophotic cavities, hydrophotic area, steric boundaries, hydrogen-acceptor site, and amino group binding site, another steric boundary near para position and a hydrogen donating site near ortho position constitute active sites of MAO-B.

• Bulletin of the Korean Chemical Society
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• v.32 no.12
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• pp.4397-4402
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• 2011

The NF-${\kappa}B$ system of transcription factors plays a crucial role in inflammatory diseases, making it an important drug target. We combined quantitative structure activity relationships for predicting the activity of new compounds and quantitative dynamic models for the NF-${\kappa}B$ network with intracellular concentration models. GFA-MLR QSAR analysis was employed to determine the optimal QSAR equation. To validate the predictability of the $IKK{\beta}$ QSAR model for an external set of inhibitors, a set of ordinary differential equations and mass action kinetics were used for modeling the NF-${\kappa}B$ dynamic system. The reaction parameters were obtained from previously reported research. In the IKKb QSAR model, good cross-validated $q^2$ (0.782) and conventional $r^2$ (0.808) values demonstrated the correlation between the descriptors and each of their activities and reliably predicted the $IKK{\beta}$ activities. Using a developed simulation model of the NF-${\kappa}B$ signaling pathway, we demonstrated differences in $I{\kappa}B$ mRNA expression between normal and different inhibitory states. When the inhibition efficiency increased, inhibitor 1 (PS-1145) led to long-term oscillations. The combined computational modeling and NF-${\kappa}B$ dynamic simulations can be used to understand the inhibition mechanisms and thereby result in the design of mechanism-based inhibitors.

• KSCE Journal of Civil and Environmental Engineering Research
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• v.11 no.3
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• pp.11-18
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• 1991

Volatile organic compounds(VOC) present in or generated by many sources, can be toxic, mutagenic or even carcinogenic, so that control of such emissions is significant. The 6 chlorinated organic chemicals as VOC were examined in this study. Prediction of the behavior of VOC on activated carbon beds is an important part of control system design. The objective of this study was to predict gas phase sorption isotherms from physical properties and liquid phase isotherms obtained with the same adsorbent and adsorbate. One of the techniques that was investigated was quantitative structure-activity relationships(QSAR) for the predicition procedures. It was possible to estimate sorption isotherms in the gas phase($a_g$) using either connectivity index, $^2{\chi}$, and the Henry's law coefficient ($H_a$) or the solubility and the equilibrium concentration in the gas phase. As a result of study, the predictive equation based on Freundlich model for $a_g$ was ${\log}\;a_g=0.238\;^2{\chi}+0.573\;{\log}\;H_a+4.330(r^2=0.94)$. Finally, this would provide a potentially useful tool to describe and predict sorption capacity without time-consuming tests.

• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1703-1706
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• 2012

Rice blast is the most serious disease of rice due to its harmfulness and its world wide distribution. $Magnaporthe$ $grisea$ is the cause of rice blast disease and destroys rice enough to feed several tens of millions of people each year. Fungicides are commonly used to control rice blast. But $M.$ $grisea$ acquires resistance to chemical treatments by genetic mutations. 2-Phenylimino-1,3-thiazolines were proposed as a novel class of fungicides against $M.$ $grisea$ in the previous study. To develop compounds with a higher biological activity, a new series of 2-phenylimino-1,3-thiazolines was synthesized and its fungicidal activity was determined against $M.$ $grisea$. The QSAR analysis was carried out on a series of 2-phenylimino-1,3-thiazolines. The QSAR results showed the dependence of fungicidal activity on the structural and physicochemical features of 2-phenylimino-1,3-thiazolines. Our results could be used as guidelines for the study of the mode of action and further design of optimal fungicides.

• Journal of Integrative Natural Science
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• v.9 no.2
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• pp.128-135
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• 2016

5-hydroxytryptamine (serotonin) receptor ($5-HT_7R$) 7 is one of G-Protein coupled receptors, which is activated by the neurotransmitter Serotonin. After activation by serotonin, $5-HT_7$ activates the production of the intracellular signaling molecule cyclic AMP. $5-HT_7$ receptor has been found to be involved in the pathophysiology of various disorders. It is reported that $5-HT_7$ receptor antagonists can be used as antidepressant agents. In this study, we report the important structural and chemical parameters for 2-methoxyphenylpiperazinylakanamides as $5-HT_7R$ inhibitors. A 3D QSAR study based on comparative molecular field analysis (CoMFA) was performed. The best predictions were obtained for the best CoMFA model with $q^2$ of 0.594 with 6 components, $r^2$ of 0.986, Fisher value as 60.607, and an estimated standard error of 0.043. The predictive ability of the test set was 0.602. Results obtained the CoMFA models suggest that the data are well fitted and have high predictive ability. The contour maps are generated and studied. The contour analyses may serve as tool in the future for designing of novel and more potent $5-HT_7R$ derivatives.