The Korean Journal of Pesticide Science (농약과학회지)

The Korean Society of Pesticide Science (한국농약과학회)
권호 표지

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

상이한 정렬에 따른 비교분자 유사성 지수분석(CoMSIA) 방법을 이용한 새로운 2-Alkoxyphenyl-3-phenylthioisoindoline-1-one 유도체들의 살균활성에 관한 3차원적인 정량적 구조와 활성과의 관계

  • Sung, Nack-Do (Division of Applied biologies and Chemistry, College of Agriculture and Life Science, Chungnam National University) ;
  • Yoon, Tae-Yong ;
  • Song, Jong-Hwan (Cytosine Laboratory, Korea Research Institute of Chemical Technology) ;
  • Jung, Hoon-Sung (Division of Applied biologies and Chemistry, College of Agriculture and Life Science, Chungnam National University)
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 윤태용 (동방아그로(주) 연구소) ;
  • 송종환 (한국화학연구원 세포화학연구팀) ;
  • 정훈성 (충남대학교 농업생명과학대학 응용생물화학부)
  • Published : 2005.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

3D-QSAR studies for the fungicidal activities against resistance phytophthora blight (RPC; 95CC7303) and sensitive phytophthora blight (Phytopthora capsici) (SPC; 95CC7105) by a series of new 2-alkoxyphenyl-3-phenylthioisoindoline-1-one derivatives (A & B) were studieded using comparative molecular similarity indices analyses (CoMSIA) methodology. From the based on the results, the two CoMSIA models, R5 and S1: as the best models were derivated. The statistical results of the models showed the best predictability and fitness for the fungicidal activities based on the cross- validated value ($q^2=0.714{\sim}0.823$) and non cross-validated, value ($r^2_{ncv.}=0.918{\sim}0.954$), respectively. The model R5 for fungicidal activity of RPC generated from the field fit alignment and combination of electrostatic field, H-bond acceptor field and LUMO molecular orbital field. The model S1 (or S5) for fungicidal activity of SPC generated from the atom based fit alignment and combination of steric field and HOMO molecular orbital field. The models also shows that inclusion of H-bond acceptor field (A) improved the statistical significance of the models. From the based graphical analyses of CoMSIA contribution maps, it was revealed that the novel selective character for fungicidal activities between the two fungi by modify of X-sub-stituent on the N-phenyl group and R-substituent on the S-phenyl group will be able to achivement.

일련의 새로운 2-alkoxyphenyl-3-phenylthioisoindoline-1-one 유도체들의 구조 변화에 의한 저항성(RPC; 95CC7303)과 감수성(SPC; 95CC7105) 고추역병 균주(Phytopthora capsici)들의 살균활성에 대한 3차원적인 정량적 구조-활성관계(3D-QSAR)를 비교분자 유사성 지수분석(CoMSIA) 방법으로 연구하였다. 그 결과, RPC 균주는 field fit 정렬시 정전기장(E)과 수소결합 받게장(A) 및 분자궤도장(LUMO)이 조합된 조건에서 모델 R5를 그리고 SPC 균주는 atom based fit 정렬시 입체장(S)과 분자궤도장(HOMO)의 조건에서 모델 S1(또는 S5)이 가장 양호한 예측성과 적합성을 나타내는($q^2=0.714{\sim}0.823$ 및 $r^2_{ncv.}=0.918{\sim}0.954$) CoMSIA 모델이었다. 또한, RPC 균주에는 LUMO (24.4%) SPC 균주에는 HOMO(13.5%) 분자 궤도장이 그리고 두 균주에 대하여 공통적으로 수소결합 받게장(A)이 살균활성에 기여하는 특성을 나타내었다. 그리고 CoMSIA 등고도 분석결과, 두 균주에 대한 선택적인 살균활성은 N-phenyl 고리상 X-치환기와 S-phenyl 고리상 R-치환기의 구조변화로 이루어질 수 있을 것으로 판단된다.

Keywords

References

  1. Boger, P and K. Wakabayashi (1999) Peroxidizing Herbicides, Springer-Verlag Berline Heidelberg. Germany
  2. Clark, M, R. D. Cramer III, D. M Jones, D. E. Patterson and P. E. Simeroth (1990) Comparative molecular field analysis (CoMFA). 2. Toward its use with 3Dstructural databases. Tetrahedron Comput. Methodol. 3:47-59 https://doi.org/10.1016/0898-5529(90)90120-W
  3. Cramer, R. D., D. E. Patterson and J. D. Bunce (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 https://doi.org/10.1021/ja00226a005
  4. Dewar, M J. S., E. G. Zoebish, E. F. Healy and J. J. P. Stewart (1985) AM1: A new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 107:3902-3909 https://doi.org/10.1021/ja00299a024
  5. Fujita, T. (2002) Similarities in bioanalogous structural transformation patterns, Ch. 15, In Agrochemical Discovery, Insect, Weed, and Fungal control (ed Baker, D. R. and N. K. Umetsu) ACS Symposium Series No. 774. American Chemical Society, Washington. DC
  6. Klebe, G. and U. Abraham (1999) Comparative molecular similarity indices analysis (CoMSIA) to study hydrogen-bonding properties and to score combinatorial libraries. J. Comput. Aid Mol. Des. 13:1-10 https://doi.org/10.1023/A:1008047919606
  7. Klebe, G. (1993) Structural Alignment of Molecules, In 3D QSAR Drug Design, Theory, Methods and Applications, (ed. Kubinyi, H.), ESCOM. Leiden, pp.173-199
  8. Marshall, G. R., C. D. Barry, H. E. Bosshard, R. A. Dammkoehler and D. A. Dunn (1979) The conformational parameter in drug design: active analog approach. pp.205-226, In Computer-assisted drug design (ed. Olsen, E. C. and R. E. Christoffersen). American Chemical Society, Washington, D.C
  9. Pallett, K. E. (1991) Other Primary Target Sites for Herbicides, Ch.5., In Target Sites for Herbicide Action (ed. Kirkwood, R. C.), Plenum Press. New York
  10. Pallett, K. E. (1997) Herbicide target sites, recent trends and new challenges. Proceeding of Brighton Crop Protection Conference-Weeds, pp.575-578
  11. Raichurkar, A. V. and V. M. Kulkarni (2003) Understanding the antitumor activity of novel hydroxysemicarbazide derivatives as ribonucleotide reductase inhibitors using CoMFA and CoMSIA. J. Med Chem. 46:4410-4427
  12. Stahle, L. and S. Wold (1988) Multivariate data analysis and experimental design in biomedical research. Progr. Med Chem. 25:292-334
  13. Stewart, J. J. (1990) MOPAC: A semiempirical molecular orbital program. J. Comp.-Aided Mol. Design., 4(1): 1-105 https://doi.org/10.1007/BF00128336
  14. Tomlin, C. D. S. (2000) A World Compendium: The Pestiside Manual, Eleventh Ed., British Crop Protection Council, 49 Downing St., Farnham, Surrey, UK
  15. Tripos Associates, Inc., 1699 S. Hanley Road, Suite 303, St. Louis, MO 63144-2913, U.S (http://www.tripos.com/Bookshelf/qsar/)
  16. Waller, C. L. and G. R. Marshall (1993) Three-dimensional quantitative structure-activity relationship of angiotesin-converting 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 https://doi.org/10.1021/jm00068a017
  17. 강은규 (2002) 2-(5-alkoxyphenyl)-3-phenylthioisoindoline-1-one 유도체들의 제초활성에 관한 3-Thioalkoxy groups의 영향. 충남대학교 대학원 석사학위 논문
  18. 이윤정 (2003) 2N-substituted-phenylisoindoline-1-one 유도체들의 protox 저해활성에 관한 2D 및 3D-QSAR 분석. 충남대학교 대학원 석사학위 논문
  19. 성낙도, 송종환, 양숙영, 박영용 (2004a) 비교 분자장 분석(CoMFA) 방법에 따른 1-(5-methyl-3-phenyliso xazolin-5-yl)methoxy-2-chloro-4-fluorobenzene 유도체들의 protox 저해활성에 관한 이해. 한국농약과학회지 8(3):151-161
  20. 성낙도, 송종환, 박경용 (2004b) 비교분자 유사성 지수 분석(CoMSIA) 방법에 따른 1-(5-methyl-3-phenyl-iso-xazolin-5-yl)methoxy-2-chloro-4-fluorobenzene유도체들의 protox 저해활성에 관한 이해. 한국응용생명화학회지 47(4):414-421
  21. 성낙도, 윤태용, 송종환, 정훈성 (2005) 상이한 정렬에 따른 비교 분자장 분석(CoMFA) 방법을 이용한 새로운 2-alkoxyphenyl-3-phenylthioisoindoline-1-one유도체들의 살균활성에 관한 3차원적인 정량적 구조와 활성과의 관계. 한국응용생명과학회지 48(1): 82-88
  22. 유응걸, 김재녕, 송종환, 정지헌, 김진석 (1995) 제초성 N-치환된 페닐-3,4-디메칠-2-(S-치환된 티오)-5-옥소-2,5-디히드로 피롤 유도체와 그 제조방법. 대한민국 특허, 제088511호
  23. 윤태용 (2002) 2-(5-alkoxyphenyl)-3-phenylthioisoindolin-1-one 유도체의 구조와 살균활성과의 관계. 충남대학교 대학원 박사학위논문