The Korean Journal of Pesticide Science (농약과학회지)

The Korean Society of Pesticide Science (한국농약과학회)
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Quantitative Structure Toxicity Relationships (QSTR) of New Herbicidal N-phenyl-3,4-dimethylphthalide Derivatives

새로운 제초성 N-phenyl-3,4-dimethylphthalimide 유도체의 정량적인 구조와 독성과의 관계 (QSTR)

  • Sung, Nack-Do (Division of Applied Biology & Chemistry, Chung-nam National University) ;
  • Yang, Sook-Young (Division of Applied Biology & Chemistry, Chung-nam National University) ;
  • Kang, Hak-Sik (Division of Applied Biology & Chemistry, Chung-nam National University)
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 양숙영 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 강학식 (충남대학교 농업생명과학대학 응용생물화학부)
  • Published : 2002.03.30
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Abstract

Quantitative structure-toxicity relationships (QSTRs) between various physicochemical parameters of substituents in new herbicidal N-phenyl-3,4-dimethylphthalimide derivatives and their discriminate score (DS) for chronic and acute toxicities against mouse and rat evaluated using TOPKAT calculation were discussed quantitatively. From the basis on the findings, it was shown that carcinogenicities of female was higher than that of male and mouse had higher tendency than rat. The STR analyses results of Hansch-Fujita type equations suggested that mouse (female & male) and rat male except rat female are dependent on LUMO energy commonly in carcinogenicity. The selective carcinogenicity factor of two species between male mouse and female mouse is dependent on optimal value (ca. $(L)_{opt.}=5.0{\AA}$) for length of $R_2$-substituent mainly. According to Free-Wilson approach, in the case of rat male, alkyl and aryl substituents were superior and in the other case, contribution of fluoro group substituents were superior to chronic toxicity.

새로운 제초성 N-phenyl-3,4-dimethylphthalimide 유도체의 구조변화에 따른 물리-화학 파라미터와 다루어진 바 없는 TOPKAT 프로그램으로 계산된 랫트 및 마우스 등의 급만성 독성에 관한 판별점수(DS) 및 치사율과의 관계(QSTR)를 정량적으로 검토하였다. 그 결과, 발암성은 랫트보다 마우스가 그리고 수컷보다는 암컷이 높은 경향이었다. $R_2$-기만이 변화하는 조건에서 Hansch-Fujita 식을 유도한 결과, 발암성에서 랫트 암컷을 제외한 마우스(암, 수) 및 랫트 수컷은 공통적으로 LUMO 에너지가 영향을 미치는 주 요인이었으며 마우스 암컷과 수컷의 발암성에 관한 선택성 요소는 주로 $R_2$-치환기 길이의 적정값(약 $(L)_{opt.}=5.0{\AA}$)에 의존적이었다. 또한, Free-Wilson 식으로부터 $R_2$-기의 기여도는 랫트 수컷의 경우, 탄화수소로 구성된 치환체가 그리고 그 이외의 경우에는 불소 치환체들의 기여도가 우세한 경향이었다.

Keywords

References

  1. Cronin, M. T. D., J. C. Dearden, A. and J. Dobbs (1991) QSAR studies of comparative toxicity in aquatic organisms. Sci. Total Environ. 110:431-439
  2. Cronin, M. T. D. and J. C. Dearden, (1995) Review: QSAR in toxicology. I. Prediction of aquatic toxicity. Quant. Struct.-Activity Relat. 14:1-7
  3. Fujita, T. (1979) Structure Activity-Relationships., Quantitatives Approaches, The Significance in Drug Design and Mode of Action Studies, Ch.2.5, Nankodo, Tokyo
  4. Hansch, C. and A. R. Steward (1964) The use of substituent constants in the analysis of the structure activity relationships in penicillin derivatives, J. Med. Chem. 7:691-694
  5. Hansch, C and A. Leo (1979) Substituents Constants for Correlation Analysis in Chemistry and Biology pp.69 & pp.77, John Wiely & Sons, New York
  6. Hermens, J. L. M. and H. J. M. Verhaar (1995) QSARs in Environmental toxicology and chemistry, ch. 10, In Classical and Three-Dimensional QSAR in Agrochemistry (ed. Hansch, C. and T. Fujita), ACS Symposium Seris No. 606., American Chemical Society, Washington, DC
  7. Hansch, C, and A. Leo (1995) Exploring QSAR, Fundamentals and Applications in Chemistry and Biology, Ch.9., ACS Professional Reference Book, ACS. Washington, DC
  8. HDI: TOPKAT (Toxicity prediction by komputer assisted technology) (Ver.5.0). Health Designs Inc., 183 E. Main St., Rochester, New York, 14604, USA
  9. Kier, L. B. and Hall, L. H. (1986) Connectivity in Structure-Activity Analysis, Ch. 6., pp.173-178. Research Studies Press Ltd. Letchworth, England
  10. Kirkwood, R. C. (1991) Taget Site for Herbicide Action, Ch. 5., pp.133-138, Plenum Press, New York
  11. Kubinyi, H. and O. H., Kehrhahn (1976) Quantitative structure-activity relationship. I.The modified Free-Wilson approach. J. Med. Chem. 19:579-586
  12. Landis, W. G. and M. H. Yu, (1995) Introduction to Environmental Toxicology: Impacts of chemicals upon ecological systems. Ch.5. pp.102-111. Lewis publishers, London
  13. Msi onlibrary (2000) $Cerius^2$ (Release 4.5), http://www.sinica.edu.tw/_scimath/msi/cerius45/qsar/QSAR40TOC.html, Ch.4.,Theory :QSAR+Descriptor, Molecular Simulations Inc.
  14. Nirmalakhandan, N., V. Arulgnanendran, M. Moshin, B. Sun and F. Cadena, (1993) Toxicity of mixtures of organic chemicals to microorganisms. Water Res. 28:543-551
  15. Oleson, E. C. and R. E. Christofferson (1979) Computer Assisted Drug Design, 161-189, ACS Symposium Series, No. 1212, ACS, Washington, D.C.
  16. Prival, M. J. (2001) Evaluation of the TOPKAT system for predicting the carcinogenicity of chemicals. Environ. Mol. Mutagen. 37(1):55-69
  17. Pillmoor, J. B., D. K. Wright, and S. D. Lindal (1991) Herbicide discovery through rational design; Some experiences., Proceeding of Brighton Crop Protection Conference-Weeds. 857-866
  18. QSAR, http://www.chem.swin.edu.au/modules/mod4/,ACCVIP; The Australian Computational Chemistry via the lternet Project
  19. SAS (Ver. 6.12), (1996) SAS(r) Proprietary Software, SAS Institute Inc. Cary, NC., U.S.A.
  20. Song, J. H., E. K. Ryu, K. M. Kim, H. R. Kim, J. N. Kim, and J. S. Kim (1997)Herbicidal cyclohexane-1,3-dione derivatives and their preparation process. U.S. Patent No. 5,631,208
  21. Venger, B. H., C. Hansch, G., J. Hatheway and Y. U. Amrein (1979) Ames test of 1-(X-phenyl)-3,3-dialkyl triazines, A quantitative structure-activity study. J. Med. Chem. 22: 473-476
  22. 성낙도, 성민규 (1999) N-phenyl-O-phenylthionocarba mate 유도체들의 살균활성에미치는 Phenyl 치환기의 효과. 한국농약과학회지 3:29-36
  23. 성낙도, 임치환, 윤기섭, 송종환, 김형래 (2000) N-(2-fluoro-4-chloro-5-alkyloxy-phenyl)-3,4-dimethyl-2-arylth io-5-oxo-2,5-dihydroxypyrrole 유도체 중 arylthio- 치환체들의 제초활성에 관한 구조-활성관계. 한국농약과학회지 4(2):32-36
  24. 성낙도, 양숙영, 박관용 (2001) 살균성 phenylthionocarba mate 유도체들의 정량적인 구조와 독성과의 관계. 충남대 농업과학연구 28(1), 33-40
  25. 강학시 (2001) 새로운 제초성 N-치환phenyl-3,4-dimethyl phthalimide 유도체의 구조와 환경독성과의 관계. 충남대, 교육대학원 석사학위 논문