Quantitative Structure-Activity Relationships for Radical Scavenging Activities of Flavonoid Compounds by GA-MLR Technique

  • Om, Ae-Son (Department of Food & Nutrition, College of Human Ecology, Hanyang University) ;
  • Ryu, Jae-Chun (Laboratory of Cellular and Molecular Toxicology, Korea Institute of Science and Technology/University of Science and Technology) ;
  • Kim, Jae-Hyoun (Department of Health Science, School of Natural Science, Dongduk Women's University)
  • Published : 2008.06.30

Abstract

The quantitative structure-activity relationship (QSAR) of a set of 35 flavonoid compounds presenting antioxidant activity was established by means of Genetic Algorithm-Multiple Linear Regression (GA-MLR) technique. Four-parametric models for two sets of data, the 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity $(R^2=0.788,\;Q^2_{cv}=0.699\;and\;Q^2_{ext}=0.577)$ and scavenging activity of reactive oxgen species (ROS) induced by $H_2O_2 (R^=0.829,\;Q^2_{cv}=0.754\;and\;Q^2_{ext}=0.573)$ were obtained with low external predictive ability on a mass basis, respectively. Each model gave some different mechanistic aspects of the flavonoid compounds tested in terms of the radical scavenging activity. Topological charge, H-bonding complex and deprotonation processes were likely to be involved in the radical scavenging activity.

Keywords

References

  1. Waris, G. & Ahsan, H. Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 5:1-8 (2006) https://doi.org/10.1186/1477-3163-5-1
  2. Schneider, I. & Bucar, F. Lipoxygenase inhibitors from natural plant sources. I. Medicinal plants with inhibitory activity on arachidonate 5-lipoxygenase and 5-lipoxygenase/cyclooxygenase. Phytother Res 19:81-102 (2005) https://doi.org/10.1002/ptr.1603
  3. Theodoratou, E. et al. Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 16:684-693 (2007) https://doi.org/10.1158/1055-9965.EPI-06-0785
  4. Kim, H. P., Son, K. H., Chang, H. W. & Kang, S. S. Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci 96:229-245 (2004) https://doi.org/10.1254/jphs.CRJ04003X
  5. Tasdemir, D. et al. Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: In vitro, In vivo, structure-activity relationship, and quantitative structure-activity relationship studies. Antimic Agents Chemother 50:1352-1364 (2006) https://doi.org/10.1128/AAC.50.4.1352-1364.2006
  6. Cheng, Z., Ren, J., Li, Y., Chang, W. & Chen, Z. Establishment of a quantitative structure-activity relation relationship model for evaluating and predicting the protective potentials of phenolic antioxidants on lipid peroxidation. J Pharm Sci 92:475-484 (2003) https://doi.org/10.1002/jps.10301
  7. Cabrera, M. et al. Synthetic chalcones, flavanones, and flavones as antitumoral agents: Biological evaluation and structure-activity relationships. Bioorg Med Chem 15:3356-3367 (2007) https://doi.org/10.1016/j.bmc.2007.03.031
  8. Heijnen, C. G., Haenen, G. R., Vekemans, J. A. & Bast, A. Protection of flavonoids against lipid peroxidation: the structure activity relationship revisited. Free Radic Res 36:575-581 (2002) https://doi.org/10.1080/10715760290025951
  9. Kontogiorgis, A. C., Pontiki, A. E. & Hadjipavlou- Litina, D. A review on quantitative structure-activity relationships (QSARs) of natural and synthetic antioxidants compounds. Mini Rev Med Chem 5:563-574 (2005) https://doi.org/10.2174/1389557054023233
  10. Weber, K. C., Honorio, K. M., Bruni, A. T., Andricopulo, A. D. & da Silva, A. B. F. A partial least squares regression study with antioxidant. flavonoid compounds. Struct Chem 17:307-313 (2006) https://doi.org/10.1007/s11224-006-9048-7
  11. Zhang, H. Y., Sun, Y. M. & Chen, D. Z. O-H bond dissociation energies of phenolic compounds are determined. by field/inductive effect or resonance effect? A DFT study and its implication. Quant Struct-Act Relat 20:148-152 (2001) https://doi.org/10.1002/1521-3838(200107)20:2<148::AID-QSAR148>3.0.CO;2-7
  12. Trouillas, P. et al. A theoretical study of the conformational behavior and electronic structure of taxifolin correlated with the free radical-scavenging activity. Food Chem 88:571-582 (2004) https://doi.org/10.1016/j.foodchem.2004.02.009
  13. Rasulev, B. F., Abdullaev, N. D., Syrov, V. N. & Leszczynski, J. A quantitative structure-activity relationship (QSAR) study of the antioxidant activity of flavonoids. QSAR Comb Sci 24:1056-1065 (2005)
  14. van Zanden, J. J. et al. Quantitative structure activity relationship studies on the flavonoid. Biochem Pharm 69:699-708 (2005) https://doi.org/10.1016/j.bcp.2004.11.002
  15. Reis, M., Lobato, B., Lameira, J., Santos, A. S. & Alves, C. N. A theoretical study of phenolic compounds with antioxidant properties. Eur J Med Chem 42:440-446 (2007) https://doi.org/10.1016/j.ejmech.2006.11.008
  16. Khlebnikov, A. I., Schepetkin, I. A., Domina N. G., Kirpotina, L. N. & Quinn, M. T. Improved quantitative structure-activity relationship models to predict antioxidant activity of flavonoids in chemical, enzymatic, and cellular systems. Bioorg Med Chem 15: 1749-1770 (2007) https://doi.org/10.1016/j.bmc.2006.11.037
  17. Amic, D. et al. SAR and QSAR of the antioxidant activity of flavonoids. Curr Med Chem 14:827-845 (2007) https://doi.org/10.2174/092986707780090954
  18. Koleva, I. I., Van Beek, T. A., Linssen, J. P. H., de Groot, A. & Evstatieva, L. N. Screening of plant extracts for antioxidant activity: a comparative study on three testing methods. Phytochem Anal 13:8-17 (2002) https://doi.org/10.1002/pca.611
  19. Sanchez-Moreno, C. Methods used to evaluate the free radical scavenging activity in foods and biological systems. Food Sci Technol Intl 8:121-137 (2002) https://doi.org/10.1177/1082013202008003770
  20. Yamagami, C. et al. Quantitative structure-activity relationship analyses of antioxidant and free radical scavenging activities for hydroxybenzalacetones. Bioorg Med Chem Lett 14:5629-5633 (2004) https://doi.org/10.1016/j.bmcl.2004.08.052
  21. Kang, K. A. et al. Screening of antioxidant and anticancer effects from flavonoids. Cancer Prev Res 11: 235-239 (2006)
  22. Todeschini, R., Consonni, V., Mannhold, R., Kubinyi H. & Timmerman, H. HANDBOOK of MOLECULAR DESCRIPTORS. Weinheim: Wiley-VCH, 2000
  23. Todeschini, R., Consonni, V. & Pavan, M. MobyDigs: SOFTWARE for REGRESSION and CLASSIFICATION MODELS by GENETIC ALGORITHMS. In Nature-inspired methods in chemometrics: Genetic algorithms and artificial neural networks, edited by Leardi, R., Elsevier, 2003
  24. Gramatica, P. Principles of QSAR models validation: internal and external. QSAR Comb Sci 26:694-701 (2007) https://doi.org/10.1002/qsar.200610151
  25. Fortin, M. J., Dale, M. R. T. & ver Hoef, J. SPATIAL ANALYSIS in ECOLOGY. Volume 4, pp. 2051-2058. In Encyclopedia of Environmetrics (ISBN 0471 899976), edited by Abdel H, El-Shaarawi and Walter W. Piegorsch. John Wiley & Sons, Ltd, Chichester, 2002
  26. Farkas, O., Jakus, J. & Heberger, K. Quantitative structure- antioxidant activity relationships of flavonoid compounds. Molecules 9:1079-1088 (2004)
  27. Fernandez, M., Caballero, J., Helguera, A. M., Castro,E. A. & González, M. P. Quantitative structure-activity relationship to predict differential inhibition of aldose reductase by flavonoid compounds. Bioorg Med Chem 13:3269-3277 (2005) https://doi.org/10.1016/j.bmc.2005.02.038
  28. Katritzky, A. R., Mu, L., Lobano, V. S. & Karelson, M. Correlation of boiling points with molecular structure: I. A training set of 298 diverse organics and a test set of 9 simple inorganics. J Phys Chem 100: 10400-10407 (1996)
  29. Stanton, D. T. & Jurs, P. C. Development and use of charge partial surface-area structural descriptors in. computer-assisted quantitative structure property relationship studies. Anal Chem 62:2323-2329 (1990) https://doi.org/10.1021/ac00220a013
  30. Todeschini, R. & Gramatica, P. The WHIM THEORY: New 3D-molecular descriptors for QSAR in environmental modelling. SAR QSAR Environ Res 7:89-115 (1997) https://doi.org/10.1080/10629369708039126
  31. Om, A. & Kim, J. H. A quantitative structure-activity relationship model for radical scavenging activity of flavonoids. J Med Food 11:29-37 (2008) https://doi.org/10.1089/jmf.2007.048
  32. Khlebnikov, A. I. et al. Improved quantitative structure- activity relationship models to predict antioxidant activity of flavonoids in chemical, enzymatic, and cellular systems. Bioorg Med Chem 15:1749-1770 (2007) https://doi.org/10.1016/j.bmc.2006.11.037