Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
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3D-QSAR Studies of 3,5-disubstituted Quinolines Inhibitors of c-Jun N-terminal Kinase-3

  • Madhavan, Thirumurthy (Centre for Bioinformatics, Department of Biochemistry, School of life sciences, University of Madras)
  • Received : 2011.07.25
  • Accepted : 2011.08.31
  • Published : 2011.09.30
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Abstract

c-Jun N-terminal kinase-3 (JNK-3) has been shown to mediate neuronal apoptosis and make the promising therapeutic target for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and other CNS disorders. In order to better understand the structural and chemical features of JNK-3, comparative molecular field analysis (CoMFA) was performed on a series of 3,5-disubstituted quinolines derivatives. The best predictions were obtained CoMFA model ($q^2$=0.707, $r^2$=0.972) and the statistical parameters from the generated 3D-QSAR models were indicated that the data are well fitted and have high predictive ability. The resulting contour map from 3D-QSAR models might be helpful to design novel and more potent JNK3 derivatives.

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References

  1. J. M. Kyriakis, and J.Avruch, "Pp54 microtubuleassociated protein 2 kinase", J. Biol. Chem., Vol. 265, pp. 17355-17363, 1990.
  2. M. Hibi, A. Lin, T. Smeal, A. Minden, and M. Karin, "Identification of an oncoprotein and UVresponsive protein kinase that binds and potentiates the c-Jun activation domain", Genes and Development., Vol. 7, pp. 2135-2148, 1993. https://doi.org/10.1101/gad.7.11.2135
  3. V. Adler, A. Polotskaya, F. Wagner, and A. S. Kraft, "Affinity-purified c-Jun amino-terminal protein kinase requires serine/threonine phosphorylation for activity", J. Biol. Chem., Vol. 267, pp. 17001-17005, 1992.
  4. R. J. Davis, "Signal transduction by the JNK group of MAP kinases", Cell., Vol. 103, pp. 239-252, 2000. https://doi.org/10.1016/S0092-8674(00)00116-1
  5. A. M. Bode, and Z. Dong, "The functional contrariety of JNK", Molecular carcinogenesis., Vol. 46, pp. 591-598, 2007. https://doi.org/10.1002/mc.20348
  6. S. Gupta, T. Barrett, A. J. Whitmarsh, J. Cavanagh, H. K. Sluss, B. Derijard, and R. J. Davis, " Selective interaction of JNK protein kinase isoforms with transcription factors", The EMBO Journal., Vol. 15, pp. 2760-2770, 1996.
  7. M. A. Bogoyevitch, "The isoform-specific functions of the c- Jun N-terminal kinases (JNKs): differences revealed by gene targeting", Bioessays., Vol. 28, pp. 923-934, 2006. https://doi.org/10.1002/bies.20458
  8. J. H. Martin, A. A. Mohit, and C. A. Miller, "Developmental expression in the mouse nervous system of the p493F12 SAP kinase", Mol. Brain Res., Vol. 35, pp. 47-57, 1996. https://doi.org/10.1016/0169-328X(95)00181-Q
  9. C. Dong, D.D. Yang, M. Wysk, A. J. Whitmarsh, R. J. Davis, and R. A. Flavell, "Defective T cell differentiation in the absence of Jnk1", Science., Vol. 282, pp. 2092-2095, 1998. https://doi.org/10.1126/science.282.5396.2092
  10. J. M. Kyriakis, and J. Avruch, "Mammalian mitogen- activated protein kinase signal transduction pathways activated by stress and inflammation", Physiol. Rev., Vol. 81, pp. 807-869, 2001. https://doi.org/10.1152/physrev.2001.81.2.807
  11. G. Y. Zhang, and Q. G. Zhang, "Agents targeting c- Jun N-terminal kinase pathway as potential neuroprotectants", Expert Opin. Invest. Drugs., Vol. 14, pp. 1373-1383, 2005. https://doi.org/10.1517/13543784.14.11.1373
  12. J. M. A. Siddiqui and P. A. Reddy, "Small Molecule JNK (c-Jun N-Terminal Kinase) Inhibitors", J. Med. Chem., Vol. 53, pp. 3005-3012, 2010. https://doi.org/10.1021/jm9003279
  13. R. Jiang, D. Duckett, W. Chen, J. Habel, Y. Y. Ling, P. L. Grassob, and T. M. Kamenecka, "3,5-Disubstituted quinolines as novel c-Jun N-terminal kinase inhibitors", Bioorganic and Medicinal Chemistry Letters., Vol. 17, pp. 6378-6382, 2007. https://doi.org/10.1016/j.bmcl.2007.08.054
  14. R. D. Cramer, D. E. Patterson, and J. D. Bunce, "Comparative molecular field analysis (CoMFA).1. Effect of shape on binding of steroids to carrier proteins", J. Am. Chem. Soc., Vol. 110, pp. 5959-5967, 1988. https://doi.org/10.1021/ja00226a005
  15. Sybyl 8.1, Tripos Inc., St. Louis, MO 63144, USA.
  16. S. J. Cho, and A. Tropsha, "Cross-validated R2- guided region selection for comparative molecular field analysis: A simple method to achieve consistent results", J. Med. Chem., Vol. 38, pp.1060-1066, 1995. https://doi.org/10.1021/jm00007a003
  17. S. Wold, M. Sjostrom, and L. Eriksson, "PLSregression: a basic tool of chemometrics", Chemometrics and intell. lab. Sy., Vol. 58, pp. 109-130, 2001. https://doi.org/10.1016/S0169-7439(01)00155-1

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