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Three Dimensional Quantitative Structure-Activity Relationship on the Fungicidal Activities of New Novel 2-Alkoxyphenyl-3-phenylthioisoindoline-1-one Derivatives Using the Comparative Molecular Field Analyses (CoMFA) Methodology Based on the Different Alignment Approaches  

Sung, Nack-Do (Division of Applied Biologies and Chemistry, Chungnam National University)
Yoon, Tae-Yong (Research Institute, Dongbang Agro Corporation)
Song, Jong-Hwan (Cytosine Laboratory, Korea Research Institute of Chemical Technology)
Jung, Hoon-Sung (Division of Applied Biologies and Chemistry, Chungnam National University)
Publication Information
Applied Biological Chemistry / v.48, no.1, 2005 , pp. 82-88 More about this Journal
Abstract
3D QSAR studies for the fungicidal activities against resistive phytophthora blight (RPC; 95CC7303) and sensitive phytophthora blight (Phytopthora capsici) (SPC; 95CC7105) by a series of new 2-alkoxyphenyl-3-phenylthioisoindoline-1-one derivatives (X: A=propynyl & B=2-chloropropenyl) were studied using comparative molecular field analyses (CoMFA) methodology. The CoMFA models were generated from the two different alignment, atom based fit (AF) alignment and field fit (FF) alignment. The atom based alignment exhibited a higher statistical results than that of field fit alignment. The best models, A3 and A7 using combination fields of H-bond field, standard field, LUMO and HOMO molecular orbital field as additional descriptors were selected to improve the statistic of the present CoMFA models. The statistical results of the two models showed the best predictability of the fungicidal activities based on the cross-validated value $q^2\;(r^2_{cv.}=RPC:\;0.625\;&\;SPC:\;0.834)$, non cross-validated value $(r^2_{ncv.}=RPC:\;0.894\;&\;SPC:\;0.915)$ and PRESS value (RPC: 0.105 & SPC: 0.103), respectively. Based on the findings, the predictive ability and fitness of the model for SPC was better than that of the model for RPC. The fugicidal activities exhibited a strong correlation with steric $(66.8{\sim}82.8%)$, electrostatic $(10.3{\sim}4.6%)$ and molecular orbital field (SPC: HOMO, 12.6% and RPC: LUMO, 22.9%) factors of the molecules. The novel selective character for fungicidal activity between two fungi depend on the positive charge of ortho, meta-positions on the N-phenyl ring and size of hydrophilicity of a substituents on the S-phenyl ring.
Keywords
3D-QSAR; 2-alkoxyphenyl-3-phenylthioisoindoline-1-one; fungicidal activity; resistant & sensitive phytophthora blight (Phytopthora capsici); different alignment approaches; CoMFA model;
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  • Reference
1 FRAC (2002) Publications, FRAC fungicide group names and codes, Fungicide Ressistance and Action Committee/www.frac.info
2 Kang, E. K. (2002) Effect of 3-Thioalkoxy groups on the herbicidal activity of 2-(5-alkoxyphenyl)-3-phenylthioisoindoline- 1-one derivatives. MS Thesis, Chungnam National University, Daejeon, Korea
3 Anand V. Raichurkar and Vithal M. Kulkarni (2003) Understanding the antitumor activity of novel hydroxysemicarbazide derivatives as ribonucleotide reductase inhibitors using CoMFA and CoMSIA. J. Med. Chem. 46, 4419-4427   DOI   ScienceOn
4 Kerr, R. (1994) Parallel helix bundles and ion channels: molecular modeling via simulated annealing and restrained molecular dynamics. Biophys. J. 67, 1501-1515   DOI   ScienceOn
5 Purcell, W. P. and Singer, J. A. (1967) A brief review and table of semiempirical parameters used in the Huckel molecular orbital method. J. Chem. Eng. Data 122, 235-246
6 Marshall, G. R., Barry, C. D., H. E. Bosshard, R. A. Dammkoehler, D. A. Dunn (1979) In Computer-assisted drug design: The conformational parameter in drug design; active analog approach. Olsen, E. C. and Christoffersen, R. E. (eds), Ammerican Chemical Society, Washington, D.C. pp. 205-226
7 Kellogg, G. E., Semus, S. F. and Abraham, D. J. (1991) HINT: A new method of empirical hydophobic field calculation for CoMFA. J. Comput.-Aided Mol. Des. 5, 545-552   DOI   PUBMED
8 Cramer, R. D., Bunce, J. D. and Patterson, D. E. (1988) Crossvalidation, bootstrapping, and partial least squares compared with multiple regression in conventional QSAR studies. Quant. Struct. -Act. Relat. 7, 18-25   DOI
9 Sung, N. D., Ock, H. S., Chung, H. J. and Lee, Y. G. (2003) Comparative molecular field analysis (CoMFA) on the growth inhibition activity of N-sub.phenyl-3,4,5,6- tetrahydrophthalimide and N-sub. phenyl-3,4-dimethylmaleimide derivatives, Kor. J. Pesticide Sci. 7, 75-82
10 Tomlin, C. D. S. (2000) The Pesticide Manual (12th ed.), Britsh Crop Protection Council, 49 Downing Street, Farnham, Surrey GU9 7PH, UK
11 Tripos Associates, Inc., 1699 S. Hanley Road, Suite 303, St. Louis, MO 63144-2913, USA, http://www.tripos.com/Bookshelf/qsar/
12 Leonard, G. C. and Hewitt, H. G. (1998) In Chemistry and Mode of Action of Crop Ptotection Agents. The Royal Society of Chemistry. UK
13 Tanaka, S., Takahashi, M., Funaki, Y., Izumi, K., Takano, H. and Miyakado (1995) In Classical and Three-Dimensional QSAR in Agrochemistry: Hydrophobicity and Systemic Activities of Fungicidal Triazoles and Blaching Herbicidal Compounds. Hansch, C and Fujita, T. (eds.) Ch. 8., ACS Symposium Series 606, American Chemical Society, Washington, DC, USA
14 Yoon, T. Y. (2002) Quantitative structure-activity relationship (QSAR) on the fungicidal activity of 2-(5-alkoxyphenyl)-3-phenylthioisoindoline-1-one derivatives. Ph.D. Thesis, Chungnam National University, Daejeon, Korea
15 Waller, C. L. and Marshall, G. R. (1993) Three-dimensional quantitative structure- activity relationship of angiotesinconverting enzyme and thermolysin inhibitors. 11. A comparasion of CoMFA models incorporating molecular orbital fields and desolvation free energies based on active-analog and complementary-receptor-field alignment rules. J. Med. Chem. 36, 2390-2403   DOI   ScienceOn
16 Clark, M., Cramer III, R. D., Jones, D. M., Patterson, D. E. and Simeroth, P. E. (1990) Comparative molecular field analysis (CoMFA). 2. Toward its use with 3D-structural databases. Tetrahedron Comput. Methodol. 3, 47-59   DOI
17 Sung, N. D. and Song, S. S. (2003) Range of physicochemical parameters for active ingredients of fungicides and insectcides as crop protection agents. J. Kor. Soc. Agric. Chem. Biotechnol. 46, 280-284
18 Lee, Y. J. (2003) Analyses of 2D and 3D-QSARs on the protox inhibition activities of 2N-substituted-phenylisoindoline-1-one derivatives., MS Thesis, Chungnam National University, Daejeon, Korea
19 Sung, N. D., Ock, H. S., Chung, H. J. and Song, J. H. (2003) Quantitative structure- activity relationship and molecular shape similarity of the herbicidal N-substituted phenyl-3,4-dimethylmaleimide derivatives. Kor. J. Pesticide Sci. 7, 100-107
20 Klebe, G. (1993) In 3D QSAR Drug Design, Theory, Methos and Applications: Structural Alignment of Molecules ESCOM. (Kubinyi, H. ed.) Leiden. pp. 173-199
21 Cramer, R. D., Patterson, D. E. and Bunce, J. D. (1988) Comparative molecular field analysis (CoMFA), I. Effect of shape on the binding of steroids to carrier proteins. J. Am. Chem. Soc. 110, 5959-5967   DOI   ScienceOn
22 Ryu, E. G., Kim J. Y., Song, J. H., Chung, G. H. and Kim, J. S. (1995) Herbicidal N-sub.phenyl-3,4-dimethyl-2-(S-sub.thio)- 5-oxo-2,5-dihydropyrrol derivatives and their synthetic method. Korea Papent, No 088511