Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
권호 표지
DOI QR코드

DOI QR Code

HQSAR Analysis on Novel series of 1-(4-Phenylpiperazin-1-yl-2-(1H-Pyrazol-1-yl) Ethanone Derivatives Targeting CCR1

  • Balasubramanian, Pavithra K. (Departments of Bio-New Drug Development, College of Medicine, Chosun University) ;
  • Cho, Seung Joo (Departments of Bio-New Drug Development, College of Medicine, Chosun University)
  • Received : 2013.09.04
  • Accepted : 2013.09.23
  • Published : 2013.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

The chemokine receptor CCR1 a GPCR super family protein contains seven transmembrane domains. It plays an important role in rheumatoid arthritis, organ transplant rejection, Alzheimer's disease and also causes inflammation. Because of its role in disease processes, antagonism of CCR1 became an attractive therapeutic target. In the current study, we have taken a novel series of recently reported CCR1 antagonist of 1-(4-Phenylpiperazin-1-yl_-2-(1H-Pyrazol-1-yl) ethanone derivatives and performed a HQSAR analysis. The model was developed with Atom (A) and bond (B) parameters and with different set of atom counts to improve the model. The results of HQSAR showed good predictive ability in terms of $r^2$ (0.904) and $q^2$ (0.590) with 0.710 as standard error of prediction and 0.344 as standard error of estimate. The contribution map depicted the atom contribution in inhibitory effect. Compound-14 which was reported to be a highly active compound showed positive atom contribution in three R groups ($R^3$. $R^{5a}$ and $R^{2b}$) in inhibitory effect, which could be the reason why this compound is highly active compound whereas, the lowest active compound-6 showed negative contribution to inhibitory effect.

Keywords

References

  1. M. Baggiolini, "Chemokines and leukocyte traffic", Nature, Vol. 392, pp. 565-568, 1998. https://doi.org/10.1038/33340
  2. A. D. Luster, "Chemokines: chemotactic cytokines that mediate inflammation", N. Engl. J. Med., Vol. 338, pp. 436-445, 1998. https://doi.org/10.1056/NEJM199802123380706
  3. S, Segerer, P. J, Nelson, and D. Scholondorff, "Chemokines, chemokine receptors, and renal disease: from basic science to pathophysiologic and therapeutic studies", J. Am. Soc. Nephrol., Vol. 11, pp. 152-176, 2000.
  4. T. Mirzadegan, F. Diehl, B. Ebi, S. Bhakta, I. Polsky, D. McCarley, M. Mulkins, G.S. Weatherhead, J.M. Lapierre, J. Dankwardt, D. Jr Morgans, R. Wilhelm, and K. Jarnagin 'Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a common chemokine receptor motif within the helical bundle", J. Biol. Chem., Vol. 275, pp. 25562-25571, 2000. https://doi.org/10.1074/jbc.M000692200
  5. C. L. Tsou, W. Peters, Y. Si, S. Slaymaker, A. M. Aslanian, S. P. Weisberg, M. Mack, and I.F. Charo "Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites", J. Clin. Invest., Vol. 117, pp. 90-909, 2007.
  6. C. Gerard and B. J. Rollins "Chemokines and disease". Nat. Immunol., Vol. 2, pp. 108-115, 2001. https://doi.org/10.1038/84209
  7. P. M. Murphy, M. Baggiolini, I. F. Charo, C. A. Hebert, R. Horuk, K. Matsushima, L.H. Miller, J.J. Oppenheim, and C. A. Power, "International union of pharmacology. XXII. Nomenclature for chemokine receptors", Pharmacol. Rev., Vol. 52, pp. 145- 176, 2000.
  8. P. M. Murphy "International union of pharmacology. XXX. Update on chemokine receptor nomenclature", Pharmacol. Rev., Vol. 54, pp. 227-229, 2002. https://doi.org/10.1124/pr.54.2.227
  9. A. Zlotnik and O. Yoshie "Chemokines: a new classification review system and their role in immunity". Immunity. Vol. 12, pp. 121-127, 2000. https://doi.org/10.1016/S1074-7613(00)80165-X
  10. M. Imai, T. Shiota, K. Kataoka, C. M. Tarby, W. J. Moree, T. Tsutsumi, and M. Sudo, "Small molecule inhibitors of the CCR2b receptor. Part 1: discovery and optimization of homopiper-azine derivatives", Bioorg. Med. Chem. Lett., Vol. 14, pp. 5407-5411, 2004. https://doi.org/10.1016/j.bmcl.2004.08.008
  11. W. J. Moree, K. I. Kataoka, M. M. Ramirez-Weinhouse, T. Shiota, M. Imai, M. Sudo, and T. Tsutsumi, "Small molecule antagonists of the CCR2b receptor. Part 2: discovery process and initial structure-activity relationships of diamine derivatives", Bioorg. Med. Chem. Lett., Vol. 14, pp. 5413-5416, 2004. https://doi.org/10.1016/j.bmcl.2004.08.009
  12. S. P. Weisberg, D. Hunter, R. Huber, J. Lemieux, S. Slaymaker, K. Vaddi, I. Charo, R. L. Leibel, and A.W. Jr. Ferrante, "CCR2 modulates inflammatory and metabolic effects of high-fat feeding", J. Clin. Invest., Vol. 116, pp. 115-124, 2006. https://doi.org/10.1172/JCI24335
  13. C. Rolland, R. Gozalbes, E. Nicolai, M.F. Paugam, L. Coussy, F. Barbosa, D. Horvath, and F. Revah, "G-protein-coupled receptor affinity prediction based on the use of a profiling dataset: QSAR design, synthesis, and experimental validation". J. Med. Chem., Vol. 48, pp. 6563-6574, 2005. https://doi.org/10.1021/jm0500673
  14. T. A. Berkhout, F. E. Blaney, A. M. Bridges, D. G. Cooper, I. T. Forbes, A. D. Gribble, P.H.E. Groot, A. Hardy, R. J. Ife, R. Kaur, K. E. Moores, H. Shillito, J. Willetts, J. Witherington, "CCR2: Characterization of the antagonist binding site from a combinedreceptor modelingmutagenesis approach", J. Med. Chem., Vol. 46, pp. 4070-4086, 2003. https://doi.org/10.1021/jm030862l
  15. T. G. Marshall, R. E. Lee, and F. E. Marshall "Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b". Theor. Biol. Med. Model., Vol. 3, p. 1, 2006. https://doi.org/10.1186/1742-4682-3-1
  16. F. L. Mendonaca, P. C. A. Fonseca, R. M. Phillips, J. W. Saldanha, T. J. Willliams, and J. E. Pease "Site-directed mutagenesis of CC chemokine receptor 1 reveals the mechanism of action of UCB 35625, a small molecule chemokine receptor antagonist", J. Biol. Chem., Vol. 280, pp. 4808-4816, 2005. https://doi.org/10.1074/jbc.M412267200
  17. N. Vaidehi, S. Schlyer, R. J. Trabanino, W. B. Floriano, R. Abrol, S. Sharma, M. Kochanny, S. Koovakat, L. Dunning, M. Liang, J. M. Fox, F. L. Mendonca, J. E. Pease, W. A. Goddard, and R. Horuk, "Predictions of CCR1 chemokine receptor structure and BX 471 antagonist binding followed by experimental validation". J. Biol. Chem., Vol. 281, pp. 27613-27620, 2006. https://doi.org/10.1074/jbc.M601389200
  18. J. Hvas, C. Mclean, J. Justesen, G. Kannourakis, L. Steinman, J. R. Oksenberg, and C. C. A. Bernard, "Perivascular T cells express the pro-inflammatory chemokine RANTES mRNA in multiple sclerosis lesions", Scand. J. Immunol., Vol. 46, pp. 195-203, 1997. https://doi.org/10.1046/j.1365-3083.1997.d01-100.x
  19. W. J. Karpus, N. W. Lukas, B. L. McRae, R. M. Strieter, S.L. Kunkel, and S.D. Miller, "An important role for the chemokine macrophage inflammatory protein-1R in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis", J. Immunol., Vol. 155, pp. 5003-5010, 1995.
  20. P. Rathanaswami, M. Hachicha, M. Sadick, T.J. Schall, and S.R. McColl "Expression of the cytokine RANTES in human rheumatoid synovial fibroblasts", J. Biol. Chem., Vol. 268, pp. 5834-5839, 1993.
  21. N. Snowden, A. Hajeer, W. Thomson, and B. Ollier, "RANTES role in rheumatoid arthritis", Lancet, Vol. 343, pp. 547-548, 1994.
  22. A. E. Koch, S. L. Kunkel, and R. M. Strieter, "Cytokine in rheumatoid arthritis", J. Invest. Med., Vol. 43, pp. 28-38, 1995.
  23. S. P. Raychauldhuri, W. Y. Jiang, E. M. Farber, T. J. Schall, M.R. Ruff, and C.B. Pert "Upregulation of RANTES in psoriatic keratinocytes: a possible pathogenic mechanism for psoriasis", Acta Derm. Venereol., Vol. 79, pp. 9-11, 1999. https://doi.org/10.1080/000155599750011615
  24. G. Kothandan, T. Madhavan, C.G. Gadhe, and S.J. Cho, "Pseudoreceptor: concept and an overview", J. Chosun Natural Sci., Vol. 3, pp. 162-167, 2010.
  25. S. J. Cho, "Recent development of search algorithm on small molecule docking", J. Chosun Natural Sci., Vol. 2, pp. 55-58, 2009.
  26. S. J. Cho, "Search space reduction techniques in small molecular docking." J. Chosun Natural. Sci., Vol. 3, pp. 143-147, 2010.
  27. S.J. Cho, "Calculation and application of partial charges", J. Chosun Natural Sci., Vol. 3, pp. 226-230, 2010.
  28. S.J. Cho, "Meaning and definition of partial charges", J. Chosun Natural Sci., Vol. 3, pp. 231-236, 2010.
  29. M. K. P. Andrew, B. A. James, S. Sen, W. Chen, Y. Xu, E. Sullivan, L. Li, K. Greenman, T. Charvat, D. Hansen, J. D. Daniel, J. J. K. Wright, and P. Zhang, "1-(4-Phenylpiperazin-1-yl_-2-(1H-Pyrazol-1-yl) ethanones as novel CCR1 antagonists". Biorganic & Medicinal Chemistry Letters, Vol. 23, pp. 1228-1231, 2013. https://doi.org/10.1016/j.bmcl.2013.01.005
  30. C. G. Gadhe, T. Madhavan, G. Kothandan, and S. J. Cho, "In silico quantitative structure-activity relationship studies on P-gp modulators of tetrahydroisoquinoline-ethyl-phenylamine series", BMC Struct. Biol., Vol. 11, p. 5, 2011. https://doi.org/10.1186/1472-6807-11-5

Cited by

  1. Ligand-Based CoMFA Study on Pyridylpyrazolopyridine Derivatives as PKCθ Kinase Inhibitors vol.7, pp.4, 2014, https://doi.org/10.13160/ricns.2014.7.4.253
  2. A CoMFA Study of Glycogen Synthase Kinase 3 Inhibitors vol.8, pp.1, 2015, https://doi.org/10.13160/ricns.2015.8.1.40
  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. 3D QSAR Study on Pyrrolopyrimidines-Based Derivatives as LIM2 Kinase Inhibitors vol.8, pp.4, 2015, https://doi.org/10.13160/ricns.2015.8.4.285
  5. A CoMFA Study of Phenoxypyridine-Based JNK3 Inhibitors Using Various Partial Charge Schemes vol.7, pp.1, 2014, https://doi.org/10.13160/ricns.2014.7.1.45
  6. 3D QSAR Studies of Mps1 (TTK) Kinase Inhibitors Based on CoMFA vol.9, pp.2, 2016, https://doi.org/10.13160/ricns.2016.9.2.113
  7. 3D-QSAR Study on Imidazopyridazines Derivatives as Potent Pim-1 Kinase Inhibitors using Region-Focused CoMFA vol.10, pp.2, 2013, https://doi.org/10.13160/ricns.2017.10.2.95