Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
권호 표지

Molecular Holographic QSAR Analysis on the Bonding Affinity Constants between Nicotin Acetylcholine Receptors and New 3-Benzylidenemyosmine Analogues and Molecular Design

새로운 3-Benzylidenemyosmine 유도체와 Nicotin Acetylcholine 수용체 사이의 결합 친화력 상수에 관한 HQSAR 분석과 분자설계

  • Jang, Seok-Chan (Division of Applied Biologies and Chemistry, College of Agriculture and Life Science, Chungnam National University) ;
  • Sung, Nack-Do (Division of Applied Biologies and Chemistry, College of Agriculture and Life Science, Chungnam National University)
  • 장석찬 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학부)
  • Published : 2007.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The molecular design and holographic (H) quantitative structure-activity relationships (HQSARs) on the binding affinity constants between new 3-benzylidenemyosmine analogues and nicotin acetylcholine receptors (nAChRs) of American cockroach (Periplaneta. americana L.) were studied quantitatively. The optimized HQSAR model (IV-2) for the binding affinity constants was derived from fragment distinction of hydrogene atoms in fragment size, 5${\sim}$8 bin. The statistical results of the HQSAR model (IVI-2) exhibited the best predictability and fitness for the binding affinity constants based on the cross-validated value (q$^2$=0.507) and non cross-validated value (r$^2_{nev.}$=0.944). From the graphical analyses of atomic contribution maps, it was revealed that the binding affinity constants depends upon the anabaseine ring in molecule and the most active compounds were designed by optimized HQSAR model (VI-2).

일련의 새로운 3-benzylidenemyosmine 유도체들의 구조 변화와 미국 바퀴벌래(Periplaneta. americana L.)의 nicotin acetylcholine 수용체 (nAChRs) 사이의 결합 친화력 상수에 관한 정량적인 구조와 활성과의 관계를 분자 홀로그램(H) QSAR 방법으로 검토하였다. 친화력 상수에 관하여 가장 양호한 HQSAR 모델은 분자조각 크기 5${\sim}$8 bin 조건에서 유도된 모델(IV-2)이었다. HQSAR 모델(VI-2)은 높은 예측성(q$^2$=0.507)과 상관성(r$^2_{nev.}$=0.944)에 근거하여 양호한 통계값들을 나타내었다. 그리고 HQSAR 기여도로부터 결합 친화력 상수는 분자내 anabaseine 고리에 의존적이었으며 결합 친화력성이 높은 화합물들이 최적화된 모델(VI-2)에 의하여 설계되었다.

Keywords

References

  1. Levin, E. D. and Simon, B. B. (1998) Nicotinic acetylcholine involvement in cognitive function in animals, Psychopharmacology (Berlin). 138, 217-230 https://doi.org/10.1007/s002130050667
  2. Kem, W. R., Mahnir, V. M., Papke, R. L. and Lingle, C. J. (1997) Anabasine is a potent agonist on muscle and neuronal alpha-bungarotoxin-sensitive nicotinic receptors. J. Pharmacol. Exp. Ther. 283, 979-992
  3. Sung, N. D., Kim, D. W. and Jung, H. S. (2005) Molecular holographic QSAR model on the herbicidal activities of new 2- (4-(6-chloro-2-benzoxazolyloxy)phenoxy)-N-phenylpropionamide derivatives and prediction of higher activity compounds. Korean J. pesticide Sci., 9, 279-286
  4. Kubinyi, H. (1993) 3D-QSAR Drug Design, Theory, Methods and Applications, ESCOM. Leiden
  5. Sung, N. D., Jang, S. C. and Choi, K. S. (2006) CoMFA and CoMSIA on the neuroblocking activity of 1-(6-chloro-3- pyridylmethyl)-2-nitroiminoimidazolidine analogues. Bull. Korean Chem. Soc., 27, 1741-1746 https://doi.org/10.5012/bkcs.2006.27.11.1741
  6. Sung, N. D., Yu, S. J. and Kang, M. S. (1997) Kinetics and mechanism of hydrolysis insecticidal imidacloprid. Agri. Chem. & Biotech., 40, 53-57
  7. Sung, N. D., Kang, M. S., Jang, H. S. and Kim, D. W. (1996) Influence of 3-N-substituents (R) on the insecticidal activities of imidacloprid and its analogues. Agric. Chem. & Biotechnol., 39, 140-146
  8. Lowis, D. R. (1997) HQSAR. A new, highly prediction QSAR technique. Tripos Technical Notes, Vol. 1., No. 5
  9. Ikeda, I., Utsunomiya, T., Sadamitsu, M., Ozoe, Y. and Mochida, K. (2006) Affinity of 3-benzylidene- and 3-cinnamylidenemyosmine analogues for periplaneta americana nicotinic acetylchloline receptors. J. Pestic Sci. 31, 417-419 https://doi.org/10.1584/jpestics.G06-11
  10. Heritage, T. W. and Lowis, D. R. (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
  11. Stahle, L. and S. Wold (1988) Multivariate data analysis and experimental design in biomedical research, Progr. Med. Chem. 25, 292-334
  12. Tripos Associates, Inc., 1699 S. Hanley Road, Suite 303, St. Louis, MO. 63144-2913, USA
  13. Chapman, N. B. and Shorter, J. (1978) Correlation Analysis in Chemistry: Recent Advances. Plenum Press. New York and London
  14. Tomizawa, M. and Yamamoto, I. (1993) Structure activity relationships of nicotinoids and imidacloprid analogues. J. Pesticide Sci., 18, 91-98 https://doi.org/10.1584/jpestics.18.91
  15. RAC: IRAC (2002) Mode of action classification, Insecticide ressistance action committee, Plantprotection. Org. IRAC
  16. Sung, N. D. and Song, S. S. (2003) The range of physicochemical parameters for the active ingredients of fungicides and insecticides as crop protection agents. J. Korean Soc. Agric. Chem. Biotechnol. 46, 280-284