Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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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

상이한 정렬에 따른 비교 분자장 분석(CoMFA) 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, 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)
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 윤태용 (동방 아그로(주) 연구소) ;
  • 송종환 (한국화학연구원 세포화학연구팀) ;
  • 정훈성 (충남대학교 농업생명과학대학 응용생물화학부)
  • Published : 2005.03.31
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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.

새로운 2-alkoxyphenyl-3-phenylthioisoindoline-1-one 유도체(A & B)들의 치환기 변화에 따른 저항성(RPC; 95CC7303)과 감수성(SPC; 95CC7105) 고추역병 균주(Phyto pthora capsici)들의 살균활성에 대한 3차원적인 정량적 구조-활성관계(3D-QSAR)를 비교 분자장 분석(CoMFA) 방법으로 연구하였다. 정렬방법에 따라 field fit(FF) 보다는 atom based fit(AF) 정렬시에 양호한(AF>FF) 모델, A3 및 A7을 얻을 수 있었다. AF 정렬시, 부가적 설명인자로서 HOMO 및 LUMO 분자 궤도장이 추가된 H-bond와 standard field에서 유도된 균주별 두 모델의 cross-validated $r^2\;_{cv.}$값$(q^2=0.625{\sim}0.834)$과 non cross-validated 값$(r^2_{ncv.}=0.894{\sim}0.915)$에 근거하여 SPC 균주의 살균활성에 대한 모델, A7이 RPC 균주의 살균활성에 대한 모델, A3보다 양호한 예측성(q2)을 나타내었다. 두 균주에 대한 살균활성은 분자의 입체장$(66.8{\sim}82.8%)$, 정전기장$(10.3{\sim}4.6%)$ 그리고 분자 궤도장(SPC: HOMO, 12.6% 및 RPC: LUMO, 22.9%)이 영향을 미치는 중요한 요소이었다. 두 균주에 대한 선택성은 N-phenyl 고리상 ortho, meta-위치의 양하전과 S-phenyl 고리상 치환기의 친수성의 크기에 의존적이었다.

Keywords

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