3D-QSAR Analysis on the Photosystem II Inhibition Activity of 6-Bromobenzo[4,5]imidazo[$1,2{\alpha}$]pyridin-8,9-dione Analogues

6-Bromobenzo[4,5]imidazo[$1,2{\alpha}$pyridin-8,9-dione 유도체들의 Photosystem II 저해활성에 관한 3D-QSAR 분석

  • Kim, Se-Gon (Division of Applied Biology & Chemistry, College of Agriculture and Life Sciences, Chungnam National University) ;
  • Cho, Yun-Gi (Division of Applied Biology & Chemistry, College of Agriculture and Life Sciences, Chungnam National University) ;
  • Hwang, Tae-Yeon (Division of Applied Biology & Chemistry, College of Agriculture and Life Sciences, Chungnam National University) ;
  • Sung, Nack-Do (Division of Applied Biology & Chemistry, College of Agriculture and Life Sciences, Chungnam National University)
  • 김세곤 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 조윤기 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 황태연 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학부)
  • Published : 2008.03.31


3D-QSAR on the inhibitory activities of 6-bromobenzo-[4,5]imidazo[$1,2{\alpha}$]-pyridin-8,9-diones analogues as substrate molecule were studied quantitatively using CoMFA and CoMSIA methods. The statistical values of CoMFA model was better predictability and fitness than CoMSIA model. The inhibitory activities according to the optimized CoMFA 2 model were dependent on the steric field (90.4%). From the CoMFA contour maps, it is found that the branched side chain as R-group will be directly attached to the carbon atom (ipso carbon) of substituent, the inhibitory activities had expected to increase. The positive charge favor groups were placed in the position between imidazol ring and pyridine ring, the inhibitory activities would increase. And if the groups of liner type will be substituted, hydrophilic favor group would raise inhibitory activities.


6-Bromobenzo[4,5]imidazo[$1,2{\alpha}$;]pyridin-8,9-diones;CoMFA;CoMSIA;3D-QSAR;photosystem II inhibitory activity


  1. Man, X., A. Zhang, S. Han and L. Wang (2002) Studies of 3D-Quantitative Structure-Activity Relationships on a set of nitroaromatic compounds: CoMFA, advanced CoMFA and CoMSIA, Chemosphere. 48:707-715 https://doi.org/10.1016/S0045-6535(02)00165-0
  2. McConnell, I. L., M. R. Badger, T. Wydrzynski and W. Hillier (2007) A quantitative assessment of the carbonic anhydrase activity in photosystem II, Biochimica Biophysica Acta. 1767:639-647 https://doi.org/10.1016/j.bbabio.2007.01.019
  3. Oettmeier, W. (1999) Herbicide resistance and supersensitivity in photosystem II, CMLS Cellular and Molecular Life Sciences, 1256-1277
  4. Wold, S., E. Johansson and M. Cocchi (1993) In 3D-QSAR in Drug Design. PLS: Parti al Least-Squares Projections to Latent Structures. (Kubinyi, H. ed.), ESCOM, Leiden. pp. 523-554
  5. Folkers, G., A. Merz and D. Rognan (1993) In 3D-QSAR in Drug Design. CoMFA: Scope and Limitations. (Kubinyi, H. ed.), ESCOM, Leiden. pp. 583-618
  6. Krivanek, R., J. Kern, A. Zouni, H. Dau and M. Haumann (2007) Spare quinones in the QB cavity of crystallized photosystem II from Thermosynechococcus elongatus, Biochimica et Biophysica Acta. 1767:520-527 https://doi.org/10.1016/j.bbabio.2007.02.013
  7. Reddy, M. R. and A. L. Parrill (1999) Overview of rational drug design. In Rational Drug, (ed. Eddy, M. R. and Parrill). Ch. 1., ACS Symposium Series. 719:1-11
  8. Apostolova, E., T. Markova, T. Filipova and M. T. Molina (2003) Influence of substituted 1,4-anthraquinones on the chlorophyll fluorescence and photochemical activity of pea thylakoid membranes, J. Photochem. Photobiol. B Biology. 70:75-80 https://doi.org/10.1016/S1011-1344(03)00057-5
  9. Okubo, T., T. Noguchi (2007) Selective detection of the structual change upon photoreactions of several redox cofactors in Photosystem II by means of light-induces ATR-FTIR difference spectroscopy, Spectrochimica Acta Part A. 66:863-868 https://doi.org/10.1016/j.saa.2006.05.001
  10. Hiraki, M., W. J. Vredenberg, van J. J. Rensen and Ko. Wakabayashi (2004) A modified fluorometric method to quantify the concentration effect ($pI_{50}$) of photosystem, Pestic. Biochemi. Physiol. 80:183-191 https://doi.org/10.1016/j.pestbp.2004.07.006
  11. Oettmeier, W., K. Masson and H. J. Hecht (2001) Heterocyclic ortho-quinones, a novel type of Photosystem II inhibitors, Biochimica et Biophysica Acta. 1504:346-351 https://doi.org/10.1016/S0005-2728(00)00263-2
  12. Vasil'ev S., G. W. Brudvig and D. Bruce (2003) The X-ray structure of photosystem II reveals a novel electron transport pathway between P680, cytochrome b559 and the energy-quenching cation. $Chl_Z^+$, FEBS Letters. 543:159-163 https://doi.org/10.1016/S0014-5793(03)00442-3
  13. Oettmeier, W., J. Jager and K. Masson (2006) Inhibition of photosystem II electron transport by acyl derivatives of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid), Biochimica et Biophysica Acta. 1757:727-729 https://doi.org/10.1016/j.bbabio.2006.05.009
  14. Dudekula, S., M. Fragata (2006) Investigation of the electron transfer site of p-benzoquinone in isolated Photosystem II particles and thylakoid membranes using $\alpha$ and $\beta$-cyclodextrins, J. Photochem. Photobiol. B; Biology. 85:177-183 https://doi.org/10.1016/j.jphotobiol.2006.07.003
  15. Loll, B., J. Kern, W. Saenger, A. Zouni and J. Biesiadka (2005) Towards complete cofactor arrangement in the 3.0 A resolution structure of photosystem II Nature. 438:1040-1044 https://doi.org/10.1038/nature04224
  16. Roberts, A. G., W. Gregor, R. D. Britt and D. M. Kramer (2003) Acceptor and donor-side interactions of phenolic inhibitors in Photosystem II. Biochimica et Biophysica Acta. 1604:23-32 https://doi.org/10.1016/S0005-2728(03)00021-5
  17. Rochaix, J. D. (2007) Role of thylakoid protein kinases in Photosynthetic acclimation, FEBS Letters. 581:2768-2775 https://doi.org/10.1016/j.febslet.2007.04.038
  18. Sung, N. D., M. K. Soung, J. W. You and S. C. Jang (2006) Comparative molecular field analysis on the fungicidal activity of N-phenylthionocarbamate derivatives based on different approaches. Korean J. Pestic. Sci. 10:157-164
  19. Reil, E., G. Hofle, W. Draber and W. Oettmeier (2001) Quinones and their N-oxides as inhibitors of photosystem II and the cytochrome $b_6/f$-complex. Biochimica et Biophysica Acta. 1506:127-132 https://doi.org/10.1016/S0005-2728(01)00189-X
  20. Zhu, X. G., Govindjee, N. R. Baker, E. Desturler, D. R. Ort and S. P. Long (2005) Chlorophyll $\alpha$ fluorescence induction kinetics in leaves predicted from a model describing each discrete step of excitation energy and electron transfer associated with photosystem II. Planta. 223:114-133 https://doi.org/10.1007/s00425-005-0064-4