DOI QR코드

DOI QR Code

A CoMFA Study of Glycogen Synthase Kinase 3 Inhibitors

  • Balupuri, Anand (Departments of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Balasubramanian, Pavithra K. (Departments of Biomedical Sciences, College of Medicine, Chosun University) ;
  • Cho, Seung Joo (Departments of Biomedical Sciences, College of Medicine, Chosun University)
  • 투고 : 2015.03.03
  • 심사 : 2015.03.25
  • 발행 : 2015.03.30

초록

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that has recently emerged as a promising target in drug discovery. It is involved in multiple cellular processes and associated with the pathogenesis of several diseases. A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed on a series of GSK-3 inhibitors to understand the structural basis for inhibitory activity. Comparative molecular field analysis (CoMFA) method was used to derive 3D-QSAR models. A reliable CoMFA model was developed using ligand-based alignment scheme. The model produced statistically acceptable results with a cross-validated correlation coefficient ($q^2$) of 0.594 and a non-cross-validated correlation coefficient ($r^2$) of 0.943. Robustness of the model was checked by bootstrapping and progressive scrambling analysis. This study could assist in the design of novel compounds with enhanced GSK-3 inhibitory activity.

키워드

참고문헌

  1. S. Frame, P. Cohen, and R. M. Biondi, "A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation", Mol. Cell, Vol. 7, pp. 1321-1327, 2001. https://doi.org/10.1016/S1097-2765(01)00253-2
  2. N. Embi, D. B. Rylatt, and P. Cohen, "Glycogen synthase kinase-3 from rabbit skeletal muscle", European journal of biochemistry, Vol. 107, pp. 519-527, 1980.
  3. S. E. Nikoulina, T. P. Ciaraldi, S. Mudaliar, P. Mohideen, L. Carter, and R. R. Henry, "Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes", Diabetes, Vol. 49, pp. 263-271, 2000. https://doi.org/10.2337/diabetes.49.2.263
  4. E. Planel, X. Sun, and A. Takashima, "Role of GSK-$3{\beta}$ in Alzheimer's disease pathology", Drug Develop. Res., Vol. 56, pp. 491-510, 2002. https://doi.org/10.1002/ddr.10100
  5. C. J. Phiel and P. S. Klein, "Molecular targets of lithium action", Annu. Rev. Pharmacol., Vol. 41, pp. 789-813, 2001. https://doi.org/10.1146/annurev.pharmtox.41.1.789
  6. M. K. Rowe, C. Wiest, and D.-M. Chuang, "GSK-3 is a viable potential target for therapeutic intervention in bipolar disorder", Neurosci. Biobehav. R., Vol. 31, pp. 920-931, 2007. https://doi.org/10.1016/j.neubiorev.2007.03.002
  7. R. S. Jope and M.-S. Roh, "Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions", Curr. Drug Targets, Vol. 7, pp. 1421-1434, 2006. https://doi.org/10.2174/1389450110607011421
  8. M. P. Mazanetz and P. M. Fischer, "Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases", Nat. Rev. Drug Discov., Vol. 6, pp. 464-479, 2007. https://doi.org/10.1038/nrd2111
  9. R. G. Gentles, S. Hu, and G. M. Dubowchik, "Recent advances in the discovery of GSK-3 inhibitors and a perspective on their utility for the treatment of Alzheimer's disease", Annu. Rep. Med. Chem., Vol. 44, pp. 3-26, 2009. https://doi.org/10.1016/S0065-7743(09)04401-7
  10. M. Aoki, M. Iwamoto-Sugai, I. Sugiura, C. Sasaki, T. Hasegawa, C. Okumura, S. Sugio, T. Kohno, and T. Matsuzaki, "Expression, purification and crystallization of human tau-protein kinase I/glycogen synthase kinase-$3{\beta}$", Acta Crystallogr. D, Vol. 56, pp. 1464-1465, 2000. https://doi.org/10.1107/S0907444900010386
  11. B. Bax, P. S. Carter, C. Lewis, A. R. Guy, A. Bridges, R. Tanner, G. Pettman, C. Mannix, A. A. Culbert, M. J. Brown, D. G. Smith, and A. D. Reith, "The structure of phosphorylated GSK-$3{\beta}$ complexed with a peptide, FRATtide, that inhibits ${\beta}$-catenin phosphorylation", Structure, Vol. 9, pp. 1143-1152, 2001. https://doi.org/10.1016/S0969-2126(01)00679-7
  12. G. Gentile, G. Merlo, A. Pozzan, G. Bernasconi, B. Bax, P. Bamborough, A. Bridges, P. Carter, M. Neu, G. Yao, C. Brough, G. Cutler, A. Coffin, and S. Belyanskaya, "5-Aryl-4-carboxamide-1,3-oxazoles: potent and selective GSK-3 inhibitors", Bioorg. Med. Chem. Lett., Vol. 22, pp. 1989-1994, 2012. https://doi.org/10.1016/j.bmcl.2012.01.034
  13. A. Balupuri and S. J. Cho, "Exploration of the binding mode of indole derivatives as potent HIV-1 inhibitors using molecular docking simulations", J. Chosun Natural Sci., Vol. 6, pp. 138-142, 2013. https://doi.org/10.13160/ricns.2013.6.3.138
  14. P. K. Balasubramanian, A. Balupuri, and S. J. Cho, "A CoMFA study of phenoxypyridine-based JNK3 inhibitors using various partial charge schemes", J. Chosun Natural Sci., Vol. 7, pp. 45-49, 2014. https://doi.org/10.13160/ricns.2014.7.1.45
  15. P. K. Balasubramanian, A. Balupuri, and S. J. Cho, "Ligand-based CoMFA study on pyridylpyrazolopyridine derivatives as PKCe kinase inhibitors", J. Chosun Natural Sci., Vol. 7, pp. 253-259, 2014. https://doi.org/10.13160/ricns.2014.7.4.253
  16. P. K. Balasubramanian and S. J. Cho, "HQSAR analysis on novel series of 1-(4-phenylpiperazin-1-yl-2-(1H-Pyrazol-1-yl) ethanone derivatives targeting CCR1", J. Chosun Natural Sci., Vol. 6, pp. 163-169, 2013. https://doi.org/10.13160/ricns.2013.6.3.163
  17. S. J. Cho, "The importance of halogen bonding: a tutorial", J. Chosun Natural Sci., Vol. 5, pp. 195-197, 2012. https://doi.org/10.13160/ricns.2012.5.3.195
  18. C. G. Gadhe, G. Kothandan, and Seung Joo Cho, "Large variation in electrostatic contours upon addition of steric parameters and the effect of charge calculation schemes in CoMFA on mutagenicity of MX analogues", Mol. Simulat., Vol. 38, pp. 861-871, 2012. https://doi.org/10.1080/08927022.2012.659182
  19. SYBYLx2.1, Tripos International, 1699 South Hanley Road, St. Louis, Missouri, 63144, USA.
  20. 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
  21. S. Wold, A. Ruhe, H. Wold, and W. J. Dunn III, "The collinearity problem in linear regression. The partial least squares (PLS) approach to generalized inverses", SIAM Journal on Scientific and Statistical Computing, Vol. 5, pp 735-743, 1984. https://doi.org/10.1137/0905052

피인용 문헌

  1. Comparative Molecular Field Analysis of Pyrrolopyrimidines as LRRK2 Kinase Inhibitors vol.9, pp.1, 2016, https://doi.org/10.13160/ricns.2016.9.1.1
  2. Molecular Docking Studies of p21-Activated Kinase-1 (PAK1) Inhibitors vol.9, pp.3, 2016, https://doi.org/10.13160/ricns.2016.9.3.161
  3. A CoMFA Study of Quinazoline-based Anticancer Agents vol.8, pp.3, 2015, https://doi.org/10.13160/ricns.2015.8.3.214
  4. HQSAR Study on Substituted 1H-Pyrazolo[3,4-b]pyridines Derivatives as FGFR Kinase Antagonists vol.10, pp.2, 2015, https://doi.org/10.13160/ricns.2017.10.2.85