The Korean Journal of Pesticide Science (농약과학회지)

The Korean Society of Pesticide Science (한국농약과학회)
권호 표지

Comparative molecular field analyses (CoMFA) on the antifungal activity against phytophthora blight fungus of 3-phenylisoxazole and 3-phenyl-2,5-dihydroisoxazol-5-one derivatives

고추 역병균에 대한 3-phenylisoxazole과 3-phenyl-2,5-dihydroisoxazol-5-one 유도체들의 살균 활성에 관한 비교 분자장 분석 (CoMFA)

  • Sung, Nack-Do (Division of Applied Biology & Chemistry, College of Agriculture & Life Sciences, Chungnam National University) ;
  • Lee, Hee-Chul (Dongbu Fine Chemicals Co., Chungchung Province Technology Diffusion Center)
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 이희철 (동부정밀화학 (주) 충청기술보급센타)
  • Published : 2002.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

3D-QSAR between fungicidal activitives ($pI_{50}$) against metalaxyl-sensitive (SPC: 95CC7105) or metalaxyl-resisitant (RPC: 95CC7303) isolate of phytophthora blight fungus (Phytophthora capsici), and a set of 3-phenylisoxazole (A) and 3-phenyl-2,5-dihydroisoxazole (B) derivatives as substrates were conducted using comparative molecular field analyses (CoMFA). The antifungal activities of (A) were generally higher than those of (B). And it is assumed that the most stable conformation of the active substrate was approximately planar from conformational search. The CoMFA models proved a good predictive ability and suggested that the electronic field of substrates were higher than hydropohobic field and steric field requirements for recognition forces of the receptor site. And the factors were strongly correlated (cross-validated $q^2>0.570$ & conventional $r^2>0.968$) with the fungicidal activitives. According to the CoMFA analyses, the selectivity factors for RPC suggested that the sterically bulky groups (C14 & C15) and electron withdrawing groups (C15 & C16) have to be introduced to the ortho, meta and para-position on the benzoyl moiety of substrates.

일련의 3-phenyl-2,5-dihydroisoxazol-5-one(A)과 3-phenylisoxazole(B)유도체 중, 치환-phenyl기가 변화함에 따라 metalaxyl 살균제에 대하여 감수성(SPC:95C C7105)이나 저항성(RPC: 95CC7303)을 나타내는 고추역병균(Phytophthora capsici)의 살균활성 에 관한 비교 분자장 분석(CoMFA) 결과를 검토하였다. 살균활성은 (A)가 (B)보다 큰 경향이었으며 활성을 나타내는 가장 안정한 기질 분자의 형태는 평면성에 가까운 구조이었다. 두 균주를 대상으로 살균 활성에 미치는 CoMFA 장을 계산한 바, 상대적인 기여도는 공히, 정전기장이 가장 우세하였고 소수성장 및 입체장은 비슷한 정도로 기여하였다. 또한, CoMFA 모델은 좋은 상관성과 높은 예측성($q^2>0.570$ 및 $r^2>0.968$)을 나타내었다. 등고도 분석으로부터 RPC에 대한 살균활성의 선택성 요소는 benzoyl-기의 ortho, meta(C14 및 C15) 위치에는 부피가 큰 치환체를 그리고 meta, para(C15 및 C16) 위치부근에는 음하전을 생성하는 전자끌게가 도입되어야 할 것으로 판단된다.

Keywords

References

  1. Cramer, R. D. III, J. D. Bunce, D. E. Patterson and I. E. Frank (1988) Cross-validation, bootstrapping, and partial least squares compared with multiple regression in conventional QSAR studies. Quantum. Struct. Act. Relat. 7:18-25
  2. Cramer, R. D. III, S. A. Deprivers, D. E. Patterson and D. E. P. Hecht (1993) Comparative molecular field analysis. pp. 443-485, In 3D QSAR Drug Design. Theory, Methods and Applications. (ed Kubinyi, H,) ESCOM, Leiden
  3. Erwin, D. C. and O. K. Ribeiro (1996) Phytophthora Diseases World-wide. The American Phytopathological Society, APS press, St. Paul
  4. Gasteiger, J. and M. Marsili (1980) Iterative partial equalization of orbital electronegativity-A rapid acess to atomic charges. Tetrahedron.. 36:3219-3228
  5. Georgopoulos, S. G. and A. C. Grigoriu (1981) Metalaxyl- resistant strains of Pseudoperonospora cubenSl’s in cucumber in green-houses of southern green, Plant Dis. 65:72 9-731
  6. Gerritsms, O. C. M., J. Ideler, K. Pie and G. C. M. Velthuis (1988) Antifungal modes of action of metalaxyl, cyprofuram, benalaxayl and oxadixyl in phenyl amide-sensitive and phenylamide-resistance strains of Phytophthora megaspermas f. sp. medicaginis and Phytophthora infestans, Crop. Prot. 7:347-355
  7. Goodford, P. J. (1985) A computational procedure for determining energgetically favorable binding site on biologically important macromolecules, J. Med. Chem. 28:849-857
  8. HDI: Health Design Inc., 183 W. Main St., Rochester, New York, 14604. U.S.A.
  9. Kim, K. H. (1993) Comparison of classical and 3D QSAR. pp. 619-642, In 3D QSAR Drug Design. Theory, Methods and Applications. (ed. Kubinyi, H.) ESCOM, Leiden
  10. Kellog, G. E. and D. J. Abraham (1992) KEY, LOCK, and LOCKSMITH: Complementary hydrophatic map predictions of drug structure from a known receptor-receptor structure from known drugs, J. Mol. Graph. 10:212-217
  11. Klebe, G. (1993) Structural alignment of molecule. pp.173-199. In 3D QSAR Drug Design. theory, Methods and Applications. (ed. Kubinyi, H.) ESCOM, Leiden
  12. Kubinyi, H. (1993) QSAR: Hansch Analysis and Related Approaches. Ch. 3-5., VCH, New York
  13. Lang, S. A. and Y. I. Lin (1984) Isoxazoles and their benzo derivatives, pp. 130, In Comprehensive Heterocyclic Chemistry (ed. Katritzky, A. R. and Rees, C. W.), Pergamon Press, New York
  14. Sakhaikar, S. S., G. M. Khandekar, S. D. Sahasrabudhe, C. K. Rao and D. C. Lathbury (1995) Herbicidal 3-(hetero)aryl-4-acylisoxazole compositions and compounds. GB. 2,284,600
  15. Sorrento, L., C. Silipo and A. Vittoria (1991) Rational approach to the design of bioactive compounds: Proceedings of the European symposium on Quantitative Structure-Activity Relationships, Vol. 16., New York
  16. Stahle, L. and S. Wold. (1988) Multivariate data analysis and experimental design in biomedical research, Progr. Med. Chem. 25:292-334
  17. Summers, L. A. (1968) IsoxazoIinone fungicides, Chem. Abst., 68: 87,286y
  18. Sybyl programe (Ver. 6.5) Tripos Associates, 1699 South Hanley Road, Suite 303, St. Liyus, MO 63144, USA
  19. Tanaka, S., M. Takahashi, Y. Funaki, K. Izumi, H. Takano and M. Miyakado (1995) Hydrophobicity and systemetic activities of fungicidal triazoles and bleaching herbicidal compounds. Ch. 8., pp. 114, In Classical and Three-Dimensional QSAR in Agrochemistry (ed. Hansch, C. and T. Fujita) ACS Symposium Series 606., American Chemical Society, Washington, DC
  20. 이희철 (2001) 2-benzoyl-3-phenylisoxazol-5-one 유도체의 합성과 항균활성에 관한 2D 및 3D 구조-활성 관계, 충남대학교 대학원, 석사학위 논문
  21. 성낙도, 유성재, 이희철 (2001) 3-phenylisoxazole 및 2-benzoyl-3-phenylisoxazol-5-one 유도체의 합성 과 살균활성에 관한 구조-활성 관계, 한국농약과학회지, 5(4):20-26