• The Korean Journal of Pesticide Science
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• v.2 no.2
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• pp.16-21
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• 1998

Bis-aromatic ${\alpha},{\beta}$-unsaturated ketone derivatives represented as substrate(S) were synthesized and their fungicidal activities in vivo against rice blast(Pyricularia oryzae) and tomato leaf blight(Phytophthora infestans) were examined with the quantitative structure activity relationships(QSAR) using 3D QSAR, comparative molecular field analysis (CoMFA). The 3D CoMFA results and those of 2D QSAR were compared and the results reveal that both results show similar trend. The two important factors, steric and electronic, contribute toward the activity. We assumed that fungicidal activity for rice blast was greatly improved by increasing with positive charge of ${\beta}$-carbon and introduction of bulky derivatives into $R_{2}$ group, while that for tomato leaf blight was improved by decreasing the positive charge of ${\beta}$-carbon and introduction of smaller molecular derivative into $R_{2}$ group. The CoMFA analyses clearly demonstrate its potential in unraveling the steric and electronic features of the molecules through contour maps.

• The Korean Journal of Pesticide Science
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• v.7 no.2
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• pp.108-116
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• 2003

A series of new quinclorac family, herbicidal 3-phenyl-5-(3,7-dichloro-8-quinolinyl)-1,2,4-oxadiazole derivatives as substrate were synthesized and their growth inhibition activity $(pI_{50})$ against root and shoot of rice plant (Oryza sativa L.) and barnyard grass (Echinochloa crus-galli) were determined. And then comparative molecular field analysis (CoMFA) and molecular holographic quantitative structure- activity relationship (HQSAR) were compared in terms of their potential for predictiability. The statistical results were suggested that HQSAR based model had better predictability than CoMFA model. The selective factors to remove barnyard grass take electron withdrawing groups which can be created positive charge and steric bulky on the phenyl ring. Results revealed that the unknown 2,6-dichloro-substituent, U5 and 2,4,6-trichloro-substituent, U6(${\Delta}pI_{50}$=CoMFA: 1.18 & HQSAR: 1.82) were predicted as compound with higher activity and selectivity.

• Journal of Integrative Natural Science
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• v.10 no.4
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• pp.209-215
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• 2017

CXC chemokine receptor 2 (CXCR2) is a prominent chemokine receptor on neutrophils. CXCR2 antagonist may reduce the neutrophil chemotaxis and alter the inflammatory response because the neutrophilic inflammation in the lung diseases is found to be largely regulated through CXCR2 receptor. Hence, in the present study, Topomer based Comparative Molecular Field Analysis (Topomer CoMFA) was performed on a series of CXCR2 antagonist named pyrimidine-5-carbonitrile-6-alkyl derivatives. The best Topomer COMFA model was obtained with significant cross-validated correlation coefficient ($q^2$ = 0.487) and non cross-validated correlation coefficients ($r^2$ = 0.980). The model was evaluated with six external test compounds and its $r^2{_{pred}}$ was found to be 0.616. The steric and electrostatic contribution map show that presence of bulkier and electropositive group around cyclopropyl ring may contribute more for improving the biological activities of these compounds. The generated Topomer CoMFA model could be helpful for future design of novel and structurally related CXCR2 antagonists.

• Reproductive and Developmental Biology
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• v.30 no.1
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• pp.13-19
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• 2006

To search of new porcine pheromonal odorants for biostimulation control system technologies to improve reproductive efficiency in livestock species, the comparative molecular field analysis (CoMFA) for binding affinity constant $(p(Od)_{50})$ between porcine odorant binding protein (pOBP) and ligands of odorant 2-(cyclohexyloxy) tetrahydrofurane derivatives as substrate molecule was conducted and discussed. In the optimized CoMFA model AIV with chirality $(C_1'(R),\;C_2(S))$ in substrate molecule and atom based fit alignment (A) of odorants, the statistical results showed the best predictability of the binding affinities $(p(Od)_{50})$ based on the LOO cross-validated value $r^2_{cv}.\;(q^2=0.886)$ and non-cross-validated conventional coefficient $(r^2_{ncv}.=0.984)$. the binding affinity constants exhibited a good correlation with steric (40.8%), electrostatic (14.6%) and hydrophobic (44.6%) factors of the substrate molecules. from the analytical results of the contour maps, which may give us some valuable informations to the modification of odorants for effective binding affinity.

• Applied Biological Chemistry
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• v.51 no.1
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• pp.38-43
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• 2008

3D-QSARs on the fungicidal activity with N-phenylbenzenesulfonamide and N-phenyl-2-thienylsul-fonamide analogues (1-34) against Fusarium wilt (Fusarium oxysporum) were discussed quantitatively using CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods, respectively. Generally, the CoMFA models have better predictability and fitness than the CoMSIA models. The fungicidal activities, according to the information of the optimized CoMF A 2 model $(r^2\;_{cv.}=0.523\;&\;r^2\;_{ncv.}=0.956)$, were dependent on the electrostatic field of the N-phenylbenzenesulfonamide analogues. Therefore, from the results of graphical analyses on the contour maps with the optimized CoMFA 2 model, it is expected that the characters of $R_4-substituents$ on the N-phenyl ring as steric and positive charge favor will contribute to the fungicidal activity against Fusarium wilt.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.356.2-356.2
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• 2002

The structure of 1-phenyl-2-substituted thiourea derivatives have been studied and optimized for their cytotoxic activity. The three dimensional quantitative structure activity relationship (3D-QSAR) was investigated using comparative molecular field analysis (CoMFA). The result suggested that electrostatic and steric factors of 2-alkylureido-1-phenyl propanol derivatives were correlated well with cytotoxic activity. (omitted)

• The Korean Journal of Pesticide Science
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• v.8 no.3
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• pp.162-167
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• 2004

In recent years, the diamondback moth (DBM), Plutella xylostella has become one of the most important pests for cruciferous plants in the world. A new type of the thiophosphoryl pyrazole insecticide, called KH502. Its outstanding insecticidal activity could be effective alternative against DBM. We investigated, using the comparative molecular field analysis (CoMPA) method, The structure-activity relationship of various thiophosphorylpyrazole derivatives and structure requirement for insecticidal activity. We found, the key substructures in pyrazole derivatives, the trifluoro-methyl group and the thiophosphoryl group. Both play an important role in insecticidal activity with the binding site. The three dimensional Quantitative Structure Activity Relationship (QSAR) analysis could provide useful information for the structural requirements of pyrazole insecticide as an insecticidal and the design of a new insecticide.

• 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.

• Bulletin of the Korean Chemical Society
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• v.29 no.3
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• pp.647-655
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• 2008

Microsomal prostaglandin E2 synthase (mPGES-1) is a potent target for pain and inflammation. Various QSAR (quantitative structure activity relationship) analyses used to understand the factors affecting inhibitory potency for a series of MK886 analogues. We derived four QSAR models utilizing various quantum mechanical (QM) descriptors. These QM models indicate that steric, electrostatic and hydrophobic interaction can be important factors. Common pharmacophore hypotheses (CPHs) also have studied. The QSAR model derived by best-fitted CPHs considering hydrophobic, negative group and ring effect gave a reasonable result (q2 = 0.77, r2 = 0.97 and Rtestset = 0.90). The pharmacophore-derived molecular alignment subsequently used for 3D-QSAR. The CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Indices Analysis) techniques employed on same series of mPGES-1 inhibitors which gives a statistically reasonable result (CoMFA; q2 = 0.90, r2 = 0.99. CoMSIA; q2 = 0.93, r2 = 1.00). All modeling results (QM-based QSAR, pharmacophore modeling and 3D-QSAR) imply steric, electrostatic and hydrophobic contribution to the inhibitory activity. CoMFA and CoMSIA models suggest the introduction of bulky group around ring B may enhance the inhibitory activity.

• Archives of Pharmacal Research
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• v.27 no.10
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• pp.1001-1008
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• 2004

Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies on 59 cinnamaldehyde analogues as Farnesyl Protein Transferase (FPTase) inhibitors were investigated using comparative molecular field analysis (CoMFA) with the PLS region-focusing method. Forty-nine training set inhibitors were used for CoMFA with two different grid spacings, $2{\AA}\;and\;1{\AA}$ Ten compounds, which were not used in model generation, were used to validate the CoMFA models. After the PLS analysis, the best predictive CoMFA model showed that the cross-validated value $(r^2_{cv})$ and the non-cross validated conventional value$(r^2_{ncv})$ are 0.557 and 0.950, respectively. From the CoMFA contour maps, the steric and electrostatic properties of cinnamaldehyde analogues can be identified and verified.