The Korean Journal of Pesticide Science (농약과학회지)

The Korean Society of Pesticide Science (한국농약과학회)
권호 표지

Molecular Holographic QSAR Model on the Herbicidal Activities of New Novel 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpropionamide Derivatives and Prediction of Higher Activity Compounds

새로운 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenyl-propionamide 유도체들의 제초활성에 관한 HQSAR 모델과 높은 활성 화합물의 예측

  • Sung, Nack-Do (Division of Applied Biologies and Chemistry, College of Agriculture and Life Science, Chungnam National University) ;
  • Kim, Dae-Whang (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) ;
  • 김대황 (한국화학연구윈 생리분자 합성 연구팀) ;
  • 정훈성 (충남대학교 농업생명과학대학 응용생물화학부)
  • Published : 2005.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

The herbicidal activities against pre-emergence barnyard grass (Echinochloa crus-galli) by a series of new 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpopionamide derivatives as substrate molecule were studied using molecular holographic (H) quantitative structure activity relationships (HQSAR) methodology. From the based on the findings, the higher herbicidal active compounds are predicted by the derived HQSAR model. The best HQSAR model (VI-1) was derived from fragment distinction combination of atoms/bonds in fragment size, $7{\sim}10$bin. The herbicidal activities from atomic contribution maps showed that the activity will be able to increased according to the R-substituents variation of the N-phenyl ring and change of 6-chloro-2-benzoxazolyloxy group. Based on the results, the statistical results of the best HQSAR model (VI-1) exhibited the best pedictability and fitness for the herbicidal activities based on the cross-validated value ($q^2=0.646$) and non cross-validated value ($r^2_{ncv.}=0.917$), respectively. From the graphical analyses of atomic contribution maps, it was revealed that the lowest herbicidal activitics depends upon the 4-(6-chloro-2-benzoxazolyloxy)phenoxy group ($pred.pI_{50}=-3.20$). Particularly, the R=4-fluoro, X=isobutoxy substituent (P2) of (X)-phenoxy-N-(R)-phenylpropionamide derivative is predicted as the highest active compound ($pred.pI_{50}=9.12$).

일련의 새로운 기질 분자로서 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpropionamide 유도체들의 구조 변화와 그에 따른 발아 전, 논피 (Echinochloa crus-galli)에 대한 제초활성과의 분자 홀로그래피적(H) QSAR 관계를 연구하였다. 그 결과로부터 높은 제초활성 화합물들이 유도된 HQSAR 모델에 의하여 예측되었다. 가장 양호한 HQSAR 모델은 분자조각 크기($7{\sim}10bin$) 조건에서 유도된 모델(VI-1)이었다. 제초활성에 관한 HQSAR 모델(VI-1)은 높은 예측성($r^2_{cv.}$ 또는 $q^2=0.646$)과 상관성($r^2_{ncv.}=0.917$)에 근거하여 양호한 통계값들을 나타내었다. 그리고 HQSAR 기여도로부터 가장 낮은 제초활성은 4-(6-chloro-2-benzoxazolyloxy)phenoxy 고리($pred.pI_{50}=-3.20$)에 의존적이었다. 특히, (X)-phenoxy-N-(R)-phenylpropionamide 유도체의 R=4-fluoro, X=isobutoxy 치환체인 4-isobutoxyphenoxy-N-(4-fluorophenyl)propionamide (P2)는 가장 높은 제초활성($pred.pI_{50}=9.12$)을 나타내는 화합물로 예측되었다.

Keywords

References

  1. Arora, A., R. K. Sairam and G. C. Srivastava (2002) Oxidative stress and antioxidative system in plants, Curr. Sci. 82: 1227-1238
  2. Copping, L. G. and H. G. Hewitt (1998) Chemistry and Mode of Action of Crop Protection Agents, The Royal Society of Chemistry, London. pp.17-44
  3. Hansch, C. and A. Leo (1995) Exploring QSAR: Fundamentals and Applications in Chemistry and Biology. ACS Professional Reference Book. American Chemical Society, Washington, DC
  4. Heritage, T. W. and D. R. Lowis (1999) Molecular Hologram QSAR. Ch. 4., In Rational Drug Design; Novel Methodology and Practical Applications (ed. Parrill, A. L. and M. R. Reddy), ACS Symposium Series 719, American Chemical Society, Washington, DC
  5. Hoppe, H. H. and H. Zacher (1985) Inhibition of fatty acid biosynthesis in isolated bean and maize chloroplasts by herbicidal phenoxy-phenoxypropionnic acid derivatives and structurally related compounds. Pestic. Biochem. Physiol. 24 :298-305 https://doi.org/10.1016/0048-3575(85)90140-3
  6. Kubinyi, H. (1993) 3D QSAR Drug Design, Theory, Methos and Applications, ESCOM. Leiden
  7. Lichtenthaler, H. K. (1990) Mode of action of herbicides affecting acetyl-CoA carboxylase and fatty acid biosynthesis. Z. Naturforsch., C: J. Biosci. 45C: 521-528
  8. Lowis, D. R. (1997) HQSAR. A new, highly prediction QSAR technique. Tripos Technical Notes, Vol. 1.(5)
  9. Luo, X. Y., Y. Sunohara, and H. Matsumoto (2004) Fluazifop-butyl causes membrane peroxidation in the herbicide-susceptible broad leaf weed bristly starbur (Acanthospermum hispidum). Pesticide Biochem. & Physiol., 78:93-102 https://doi.org/10.1016/j.pestbp.2003.10.002
  10. Mager, P. P. (1988) Multivariate Chemometrics in QSAR: A Dialogue. Letchworth, Hertfordshire, England, Wiley
  11. Stahle, L. and S. Wold (1988) Multivariate data analysis and experimental design in biomedical research, Progr. Med. Chem. 25:292-334
  12. Tomlin, C. D. S. (2000) A World Compendium: The Pesticide Manual. 11th Ed., British Crop Protection Council, 49 Downing St., Farnham, Surrey, UK
  13. Tripos Associates, Inc., 1699 S. Hanley Road, Suite 303, St. Louis, MO. 63144-2913, U.S.A
  14. Zablotowicz, R. M., R. E. Hoagland, W. J. Staddon and M. A Locke (2000) Effects of pH on chemical stability and de-esterification of Fennoxaprop-ethyl by purified enzymes, bacterial extracts, and soils. J. Agric. Food Chem. 48:4711-4716 https://doi.org/10.1021/jf991062f
  15. 성낙도, 이상호, 장해성, 김대황, 김진석 (1999) 2-(4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpropionamide 유도체중 N-phenyl 치환체들에 의한 벼와 피의 선택적 제초 활성에 미치는 구조-활성관계. 한국농약과학회지 3(3):11-19
  16. 성낙도, 이상호, 류재욱, 우재춘, 구동완, 김대황 (2000a) 발아전 후 벼의 약해에 미치는 2-(4-(6-chloro-2-benz-oxazolyloxy)phenoxy)-N-phenylpropionamide 유도체들중 N-phenyl 치환기의 효과. 한국농화회지 43(1):52-56
  17. 성낙도, 이상호, 고영관, 이경모, 김대황, 김태준 (2000b) 수답에서 2-(4-6-cholro-2-benzoxazolyloxy)phenoxy)-N-phenylpropionamide 유도체중 N-phenyl 치환제들의 제초성. 한국농약과학회지 4(2):21-28
  18. 성낙도, 정훈성 (2005) 새로운 2-(4-(6-chloro-2-benzoxa-zolyloxy)phenoxy)-N-phenylpro-pionamide 유도체들의 제초활성에 관한 3차원적인 정량적 구조와 활성과의 관계. 한국응용생명화학회지 48(3):252-257