• Proceedings of the PSK Conference
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• 2003.10b
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• pp.186.3-186.3
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• 2003

The three-dimensional quantitative structure-activity relationship (3D-QSAR) study using the comparative molecular field analysis (CoMFA) was performed on indolinones derivatives as an inhibitor of the protein tyrosine kinase of fibroblast growth factor receptor (FGFR). In the training set, twenty-four indolinone derivatives were aligned based on the indole fragment and the steric and electrostatic fields were included in the analysis. The best predicted model showed the cross-validated coefficient (r$^2$$\sub$cv/) of 0.804 and bib-cross validated coefficient (r$^2$) of 0.942. The CoMFA study can be used to predict several new inhibitors of the FGFR.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.230.1-230.1
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• 2002

In this study, anti-cancer effect of N-phenyl-O-phenylthionocarbamate (PPTC) substitutes was investigated. and the apoptotic mechanism by these substrates was examined on SK-MEL -28 human skin cancer cell line. SK-MEL -28 cell was treated at various concentrations for 48hr. and then MTT assay was performed to gain IC$\sub$50/ value and examine cytotoxicity of PPTC substitutes, and quantitative structure-activity relationship (QSAR) between cell and these PPTC substitutes was examined. (omitted)

• Bulletin of the Korean Chemical Society
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• v.31 no.6
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• pp.1469-1473
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• 2010

Influences of alrylamino (R) substituents on the herbicidal activity ($pI_{50}$) of 1-(4-chloro-2-fluoro-5-propargyloxypheny)-3-(R)-thiourea analogues (1 ~ 35) against the barnyard grass (Echinochloa crusgalli) in the pre-emergence step were discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) as the three dimensional quantitative structure-activity relationship (3D-QSAR) method. The statistically most satisfactory CoMFA models for the herbicidal activity against the barnyard grass had the better predictability ($r^2{_{cv.}}$) and correlativity ($r^2{_{ncv.}}$) than those of CoMSIA models. The optimized CoMFA model 1($r^2{_{cv.}}$ = 0.531 & $r^2{_{ncv.}}$ = 0.931) with the sensitivity to the perturbation (${d_q}^{2'}{dr^2}_{yy'}$ = 1.081) and the prediction ($q^2$ = 0.475) produced by a progressive scrambling analyses were not dependent on chance correlation. And statistical qualities with the atom based fit alignment (AF) were slightly higher than those of the field fit alignment (FF). According to the optimized CoMFA model 1, the contribution ratio (%) of the steric field (76.9%) on the herbicidal activity of the Thioureas was three-fold higher than that of the electrostatic field (20.1%) and the hydrophobic field (3.0%) had the least influence. A steric favor group is on the vicinity of the nitrogen atom in alrylamino (R) substituent, and a steric disfavor group is on the outer side of alrylamino (R) substituent. Thus, as the size of alrylamino (R) substituent increases, so does the herbicidal activity of the substituent.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.159-164
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• 2007

Stimulation of epidermal growth factor receptor (EGFR) is essential in signaling pathway of tumor cells. Thus, EGFR has intensely studied as an anticancer target. We developed hologram quantitative structure activity relationship (HQSAR) models for data set which consists of tricyclic azepine derivatives showing inhibitory activities for EGFR. The optimal HQSAR model was generated with fragment size of 6 to 7 while differentiating fragments having different atom and connectivity. The model showed cross-validated $q^2$ value of 0.61 and non-cross-validated $r^2$ value of 0.93. When the model was validated with an external set excluding one outlier, it gave predictive $r^2$ value of 0.43. The contribution maps generated from this model were used to interpret the atomic contribution of each atom to the overall inhibition activity. This can be used to find more efficient EGFR inhibitors.

• Bulletin of the Korean Chemical Society
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• v.24 no.12
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• pp.1742-1750
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• 2003

In order to characterize the hydrophobic parameters of N-acetyl amino acid amides in 1-octanol/water, a theoretical calculation was carried out using a solvation free energy density model. The hydrophobicity parameters of the molecules are obtained with the consideration of the solvation free energy over the solvent volume surrounding the solute, using a grid model. Our method can account for the solvent accessible surface area of the molecules according to conformational variations. Through a comparison of the hydrophobicity of our calculation and that of other experimental/theoretical works, the solvation free energy density model is proven to be a useful tool for the evaluation of the hydrophobicity of amino acids and peptides. In order to evaluate the solvation free energy density model as a method of calculating the activity of drugs using the hydrophobicity of its building blocks, the contracture of Bradykinin potentiating pentapeptide was also predicted from the hydrophobicity of each residue. The solvation free energy density model can be used to employ descriptors for the prediction of peptide activities in drug discovery, as well as to calculate the hydrophobicity of amino acids.

• Bulletin of the Korean Chemical Society
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• v.30 no.11
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• pp.2739-2748
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• 2009

Hologram and three dimensional quantitative structure activity relationship (3D QSAR) studies for a series of anilinobipyridine JNK3 inhibitors were performed using various alignment-based comparative molecular field analysis (COMFA) and comparative molecular similarity indices analysis (CoMSIA). The in vitro JNK3 inhibitory activity exhibited a strong correlation with steric and electrostatic factors of the molecules. Using four different types of alignments, the best model was selected based on the statistical significance of CoMFA ($q_2\;=\;0.728,\;r_2\;=\;0.865$), CoMSIA ($q_2\;=\;0.706,\;r_2\;=\;0.960$) and Hologram QSAR (HQSAR: $q_2\;=\;0.838,\;r_2\;=\;0.935$). The graphical analysis of produced CoMFA and CoMSIA contour maps in the active site indicated that steric and electrostatic interactions with key residues are crucial for potency and selectivity of JNK3 inhibitors. The HQSAR analysis showed a similar qualitative conclusion. We believe these findings could be utilized for further development of more potent and selective JNK3 inhibitors.

• Bulletin of the Korean Chemical Society
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• v.25 no.12
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• pp.1801-1806
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• 2004

Ligand-based quantitative structure-activity relationship (QSAR) studies were performed on indolinones derivatives as a potential inhibitor of the protein tyrosine kinase of fibroblast growth factor receptor (FGFR) by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) implemented in the SYBYL packages. The initial X-ray structure of docked ligand (Su5402) to FGFR was used to minimize the 27 training set molecules using TRIPOS force field. Seven models were generated using CoMFA and CoMSIA with grid spacing 2 ${\AA}$. After the PLS analysis the best predicted CoMSIA model with hydrophobicity, hydrogen bond donor and acceptor property showed that a leave-one out(LOO) cross validated value $({r^2}_{cv})^$ and non-cross validated conventional value $({r^2}_{ncv})^$ are 0.543 and 0.938, respectively.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.893-900
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• 2004

2- or 6-Substituted BZT-N derivatives were synthesized, and their cytotoxic activity against can-cer L1210 and SNU-1 cells was examined. The antitumor action was also assessed in mice bearing S-180 cells in peritoneal cavity. In a comparison, it was found that 6-substituted BZT-N derivatives exhibited higher potencies in both bioactivities than 2-substituted BZT-N derivatives against L1210 cells in in vitro and S-180 in vitro tests exception of compound 36. Interestingly, it was observed that 2-substituted compound 36, which has methyl group at RI position, exhib-ited a better antitumor activity than 6-substituted compounds against L1210 and SNU-1 in vitro. The EDso value of 2-substituted compound 36 against L1210 was found to be comparable to the EDso value of adriamycin and was even better against the solid cancer cell line SNU-1. It was also observed that 2-substituted compound 36 showed better antitumor activity in mice bearing S-180 cells in the peritoneal cavity. The T/C (％) value of 2-substituted compound 36 was simi-lar to that of adriamycin. Quantitative structure-activity relationship (QSAR) tests reveal that the experimental E $D_{50}$ values against SNU-1 closely correlate with both the calculated HOMO ener-gies ( $E_{HOMO}$) and the measured H-NMR chemical shift of 3-H ($\delta$$_{H}$). The results suggests that a compound having higher $E_{HOMO}$ and $\delta$$_{H}$ values usually should have a lower E $D_{50}$ (SNU-1) value.lue.lue.lue.

• The Korean Journal of Pesticide Science
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• v.9 no.3
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• pp.199-204
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• 2005

The herbicidal activities against barnyardgrass (Echinochloa crus-galli) by R-groups on the hexahydroisoindol-1-one ring of new 2-(4-chloro-5-(2-chloroallyloxy)-2-fluorophenyl) -3-thioalkoxy-2,3,4,5,6,7-hexahydroisoindol-1-one derivatives were studied using molecular holographic quantitative structure-activity relationships (HQSAR) methodology. Based on the results, the statistical results of the optimised HQSAR model (I-2) exhibited the best predictability and fitness for the herbicidal activities based on the cross-validated value ($r^2_{cv.}$ or $q^2=0.714$) and non-cross-validated value ($r^2_{ncv.}=0.922$), respectively. From the based graphical analyses of atomic contribution maps, herbicidal activities against barnyardgrass were confirmed depends upon the C4-C6 atoms of hexahydroisoindoline-l-one ring, carbon atom of ortho-position and meta-methyl group of 3-tolylthio substituent (8).

• The Korean Journal of Pesticide Science
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• v.2 no.3
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• pp.45-51
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• 1998

A series of bis-aromatic ${\alpha},{\beta}$-unsaturated ketone derivatives with mesaured fungicidal activities in vivo against rice blast(Pyricularia oryzae), tomato leaf blight (Phytophtora infestans) and barley powdery mildew(Erysiphe graminis) were studied by using quantitative structure activity relationship equations. The QSAR model for the activity of phenyl substituents, $1{\sim}11$, clearly reveals three important factors, namely, resonance(R<0), optimal molecular hydrophobicity(${\pi})_{opt.}=0.38$) and optimal distance($((L_{1})_{opt.}=5.69({\AA}))$ of substituent, respectively. But in case of 2-pyridyl substituents, $12{\sim}28$, the activity were governed by optimal molecular refractivity $((M_{R})_{opt.}=8.04{\sim}39cm^{3}/mol)$, steric effect(Es<0) and LUMO energy(e.v). The fungicidal activity relationship of phenyl and 2-pyridyl substituents against Erysiphe graminis have been proportioned.