Molecular characterization of EP6 - A novel imidazo[1,2-a]pyridine based direct 5-lipoxygenase inhibitor

Biochemical Pharmacology

Volumn 83, Issue 2, 2012, Pages 228-240

  Wisniewska, Joanna M ^a   Rödl, Carmen B ^a   Kahnt, Astrid S ^a   Buscató, Estel La ^a   Ulrich, Sandra ^a   Tanrikulu, Yusuf ^a   Achenbach, Janosch ^a   Rörsch, Florian ^a   Grösch, Sabine ^a   Schneider, Gisbert ^b   Cinatl Jr , Jindrich ^a   Proschak, Ewgenij ^a   Steinhilber, Dieter ^a   Hofmann, Bettina ^a  

^a GOETHE UNIVERSITY   (Germany)

^b ETH ZURICH   (Switzerland)

Author keywords

5 Lipoxygenase; Inflammation; Inhibitor; Leukotrienes; Molecular modeling

Indexed keywords

ARACHIDONATE 5 LIPOXYGENASE; ARACHIDONIC ACID; CYCLOHEXYL[6 METHYL 2 (4 MORPHOLIN 4 YL PHENYL)IMIDAZO[1,2 A]PYRIDIN 3 YL]AMINE; EP 6; IMIDAZO[1,2 A]PYRIDINE DERIVATIVE; LIPOXYGENASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CELL VIABILITY; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; ENZYME ACTIVITY; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; MOLECULAR BIOLOGY; MUTAGENESIS; POLYMORPHONUCLEAR CELL; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TUMOR CELL;

ALLOSTERIC REGULATION; ANIMALS; CELL SURVIVAL; CELLS, CULTURED; HELA CELLS; HUMANS; IMIDAZOLES; LIPOXYGENASE INHIBITORS; MICE; OXIDATION-REDUCTION; PHOSPHORYLATION; PYRIDINES; SHEEP; U937 CELLS;

EID: 83955163766     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2011.10.012     Document Type: Article

References (78)

1. S.E. Dahlén, P. Hedqvist, S. Hammarström, and B. Samuelsson Leukotrienes are potent constrictors of human bronchi Nature 288 1980 484 486 (Pubitemid 11163960)
2. C.D. Funk Prostaglandins and leukotrienes: advances in eicosanoid biology Science 294 2001 1871 1875 (Pubitemid 33101574)
3. O. Werz, and D. Steinhilber Therapeutic options for 5-lipoxygenase inhibitors Pharmacol Ther 112 2006 701 718 (Pubitemid 44592614)
4. M. Peters-Golden, and W.R. Henderson Leukotrienes N Engl J Med 357 2007 1841 1854
5. B. Samuelsson, S.E. Dahlén, J.A. Lindgren, C.A. Rouzer, and C.N. Serhan Leukotrienes and lipoxins: structures, biosynthesis, and biological effects Science 237 1987 1171 1176 (Pubitemid 17131222)
6. O. Rdmark, and B. Samuelsson Regulation of the activity of 5-lipoxygenase, a key enzyme in leukotriene biosynthesis Biochem Biophys Res Commun 396 2010 105 110
7. Y. Chen, Y. Hu, H. Zhang, C. Peng, and S. Li Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia Nat Genet 41 2009 783 792
8. G.W. Carter, P.R. Young, D.H. Albert, J. Bouska, R. Dyer, and R.L. Bell 5-lipoxygenase inhibitory activity of zileuton J Pharmacol Exp Ther 256 1991 929 937
9. H.M. Berman, T. Battistuz, T.N. Bhat, W.F. Bluhm, P.E. Bourne, and K. Burkhardt The Protein Data Bank Acta Crystallogr D Biol Crystallogr 58 2002 899 907 (Pubitemid 34653017)
10. N.C. Gilbert, S.G. Bartlett, M.T. Waight, D.B. Neau, W.E. Boeglin, and A.R. Brash The structure of human 5-lipoxygenase Science 331 2011 217 219
11. X.S. Chen, and C.D. Funk The N-terminal beta-barrel domain of 5-lipoxygenase is essential for nuclear membrane translocation J Biol Chem 276 2001 811 818 (Pubitemid 32050382)
12. S. Kulkarni, S. Das, C.D. Funk, D. Murray, and W. Cho Molecular basis of the specific subcellular localization of the C2-like domain of 5-lipoxygenase J Biol Chem 277 2002 13167 13174 (Pubitemid 34952687)
13. C. Hörnig, D. Albert, L. Fischer, M. Hörnig, O. Rdmark, and D. Steinhilber 1-Oleoyl-2-acetylglycerol stimulates 5-lipoxygenase activity via a putative (phospho)lipid binding site within the N-terminal C2-like domain J Biol Chem 280 2005 26913 26921 (Pubitemid 41040726)
14. T. Hammarberg, P. Provost, B. Persson, and O. Rdmark The N-terminal domain of 5-lipoxygenase binds calcium and mediates calcium stimulation of enzyme activity J Biol Chem 275 2000 38787 38793 (Pubitemid 32009215)
15. Y.Y. Zhang, T. Hammarberg, O. Rdmark, B. Samuelsson, C.F. Ng, and C.D. Funk Analysis of a nucleotide-binding site of 5-lipoxygenase by affinity labelling: binding characteristics and amino acid sequences J Biol Chem 351 2000 3697 3707
16. O.P. Rdmark The molecular biology and regulation of 5-lipoxygenase Am J Respir Crit Care Med 161 2000 S11 S15
17. J.E. Tateson, R.W. Randall, C.H. Reynolds, W.P. Jackson, P. Bhattacherjee, and J.A. Salmon Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids: biochemical assessment in vitro and ex vivo Br J Pharmacol 94 1988 528 539
18. R.M. McMillan, and E.R. Walker Designing therapeutically effective 5-lipoxygenase inhibitors Trends Pharmacol Sci 13 1992 323 330
19. D. Steinhilber 5-Lipoxygenase: a target for antiinflammatory drugs revisited Curr Med Chem 6 1999 71 85 (Pubitemid 29068270)
20. J.F. Evans, C. Lévillé, J.A. Mancini, P. Prasit, M. Thérien, and R. Zamboni 5-Lipoxygenase-activating protein is the target of a quinoline class of leukotriene synthesis inhibitors Mol Pharmacol 40 1991 22 27
21. G.C. Crawley, R.I. Dowell, P.N. Edwards, S.J. Foster, R.M. McMillan, and E.R. Walker Methoxytetrahydropyrans. A new series of selective and orally potent 5-lipoxygenase inhibitors J Med Chem 35 1992 2600 2609
22. G.C. Crawley, M.T. Briggs, R.I. Dowell, P.N. Edwards, P.M. Hamilton, and J.F. Kingston 4-Methoxy-2-methyltetrahydropyrans: chiral leukotriene biosynthesis inhibitors, related to ICI D2138, which display enantioselectivity J Med Chem 36 1993 295 296 (Pubitemid 23060100)
23. W.G. Smith, A.F. Shaffer, J.L. Currie, J.M. Thompson, S. Kim, and T. Rao Characterization of 5-lipoxygenase inhibitors in biochemical and functional in vivo assays J Pharmacol Exp Ther 275 1995 1332 1338 (Pubitemid 26130640)
24. S.M. Nasser, G.S. Bell, R.J. Hawksworth, K.E. Spruce, R. MacMillan, and A.J. Williams Effect of the 5-lipoxygenase inhibitor ZD2138 on allergen-induced early and late asthmatic responses Thorax 49 1994 743 748 (Pubitemid 24250229)
25. C.R. Turner, W.B. Smith, C.J. Andresen, J.F. Eggler, and J.W. Watson The effect of 5-lipoxygenase inhibition on Ascaris antigen (Ag)-induced responses in atopic monkeys Inflamm Res 45 1996 42 49 (Pubitemid 26032105)
26. O. Werz, D. Szellas, M. Henseler, and D. Steinhilber Nonredox 5-lipoxygenase inhibitors require glutathione peroxidase for efficient inhibition of 5-lipoxygenase activity Mol Pharmacol 54 1998 445 451 (Pubitemid 28368835)
27. L. Fischer, D. Szellas, O. Rdmark, D. Steinhilber, and O. Werz Phosphorylation- and stimulus-dependent inhibition of cellular 5-lipoxygenase activity by nonredox-type inhibitors FASEB J 17 2003 949 951
28. M. Peters-Golden, and T.G. Brock Intracellular compartmentalization of leukotriene synthesis: unexpected nuclear secrets FEBS Lett 487 2001 323 326 (Pubitemid 32121750)
29. O. Werz, D. Szellas, D. Steinhilber, and O. Rdmark Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2) J Biol Chem 277 2002 14793 14800 (Pubitemid 34959961)
30. O. Werz, E. Bürkert, L. Fischer, D. Szellas, D. Dishart, and B. Samuelsson Extracellular signal-regulated kinases phosphorylate 5-lipoxygenase and stimulate 5-lipoxygenase product formation in leukocytes FASEB J 16 2002 1441 1443
31. D.P. Hajjar, and K.B. Pomerantz Signal transduction in atherosclerosis: integration of cytokines and the eicosanoid network FASEB J 6 1992 2933 2941
32. G.L. Johnson, and R. Lapadat Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases Science 298 2002 1911 1912 (Pubitemid 35425238)
33. J.A. Mancini, M. Abramovitz, M.E. Cox, E. Wong, S. Charleson, and H. Perrier 5-Lipoxygenase-activating protein is an arachidonate binding protein FEBS Lett 318 1993 277 281 (Pubitemid 23071752)
34. J.F. Evans, A.D. Ferguson, R.T. Mosley, and J.H. Hutchinson What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases Trends Pharmacol Sci 29 2008 72 78
35. J. Gillard, A.W. Ford-Hutchinson, C. Chan, S. Charleson, D. Denis, and A. Foster L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5- isopropylindol-2-yl]-2,2-dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitor Can J Physiol Pharmacol 67 1989 456 464 (Pubitemid 19186702)
36. P. Prasit, M. Belley, M. Blouin, C. Brideau, C. Chan, and S. Charleson A new class of leukotriene biosynthesis inhibitor: the development of MK-0591 J Lipid Mediat 6 1993 239 244
37. J.H. Hutchinson, Y. Li, J.M. Arruda, C. Baccei, G. Bain, and C. Chapman 5-Lipoxygenase-activating protein inhibitors: development of 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl] -5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid (AM103) J Med Chem 52 2009 5803 5815
38. A.P. Sampson FLAP inhibitors for the treatment of inflammatory diseases Curr Opin Investig Drugs 10 2009 1163 1172
39. B. Hofmann, L. Franke, E. Proschak, Y. Tanrikulu, P. Schneider, and D. Steinhilber Scaffold-hopping cascade yields potent inhibitors of 5-lipoxygenase ChemMedChem 3 2008 1535 1538
40. K. Groebke, L. Weber, and F. Mehlin Synthesis of imidazo[1,2-a] annulated pyridines, pyrazines and pyrimidines by a novel three-component condensation Synlett 29 1998 661 663 (Pubitemid 128694261)
41. J.J. Cinatl, R. Blaheta, M. Bittoova, M. Scholz, S. Margraf, and J.U. Vogel Decreased neutrophil adhesion to human cytomegalovirus-infected retinal pigment epithelial cells is mediated by virus-induced up-regulation of Fas ligand independent of neutrophil apoptosis J Immunol 165 2000 4405 4413
42. O. Werz Activation of 5-lipoxygenase by cell stress is calcium independent in human polymorphonuclear leukocytes Blood 99 2002 1044 1052 (Pubitemid 34527142)
43. Y.Y. Zhang, O. Rdmark, and B. Samuelsson Mutagenesis of some conserved residues in human 5-lipoxygenase: effects on enzyme activity Proc Natl Acad Sci USA 89 1992 485 489
44. A.Y. Michel, D. Steinhilber, and O. Werz Development of a method for expression and purification of the regulatory C2-like domain of human 5-lipoxygenase Protein Expr Purif 59 2008 110 116
45. T. Hammarberg, Y.Y. Zhang, B. Lind, O. Rdmark, and B. Samuelsson Mutations at the C-terminal isoleucine and other potential iron ligands of 5-lipoxygenase FEBS J 230 1995 401 407
46. M. Brungs, O. Rdmark, B. Samuelsson, and D. Steinhilber Sequential induction of 5-lipoxygenase gene expression and activity in Mono Mac 6 cells by transforming growth factor beta and 1,25-dihydroxyvitamin D3 Proc Natl Acad Sci USA 92 1995 107 111
47. T.J. Maier, L. Tausch, M. Hoernig, O. Coste, R. Schmidt, and C. Angioni Celecoxib inhibits 5-lipoxygenase Biochem Pharmacol 76 2008 862 872
48. F. Rörsch, I. Wobst, H. Zettl, M. Schubert-Zsilavecz, S. Grösch, and G. Geisslinger Nonacidic inhibitors of human microsomal prostaglandin synthase 1 (mPGES 1) identified by a multistep virtual screening protocol J Med Chem 53 2010 911 915
49. S. Thorén, and P.J. Jakobsson Coordinate up- and down-regulation of glutathione-dependent prostaglandin E synthase and cyclooxygenase-2 in A549 cells. Inhibition by NS-398 and leukotriene C4 FEBS J 267 2000 6428 6434
50. R. Schmidt, O. Coste, and G. Geisslinger LC-MS/MS-analysis of prostaglandin E2 and D2 in microdialysis samples of rats J Chromatogr B Analyt Technol Biomed Life Sci 826 2005 188 197 (Pubitemid 41446449)
51. A. Fischer, J. Metzner, S.D. Steinbrink, S. Ulrich, C. Angioni, and G. Geisslinger 5-Lipoxygenase inhibitors induce potent anti-proliferative and cytotoxic effects in human tumour cells independently of suppression of 5-lipoxygenase activity Br J Pharmacol 161 2010 936 949
52. D.M. Maron, and B.N. Ames Revised methods for the Salmonella mutagenicity test Mutat Res 113 1983 173 215 (Pubitemid 13120319)
53. T. Fechteler, U. Dengler, and D. Schomburg Prediction of protein three-dimensional structures in insertion and deletion regions: a procedure for searching data bases of representative protein fragments using geometric scoring criteria J Mol Biol 253 1995 114 131
54. J. Wang, P. Cieplak, and P.A. Kollman How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J Comput Chem 21 2000 1049 1074
55. O. Korb, T. Stützle, and T.E. Exner PLANTS: application of ant colony optimization to structure-based drug design Lect Notes Comput Sci 4150 2006 247 258 (Pubitemid 44811953)
56. M. Peters-Golden, and T.G. Brock Intracellular compartmentalization of leukotriene biosynthesis Am J Respir Crit Care Med 161 2000 S36 S40
57. R.W. Bryant, T.C. Simon, and J.M. Bailey Role of glutathione peroxidase and hexose monophosphate shunt in the platelet lipoxygenase pathway J Biol Chem 257 1982 14937 14943 (Pubitemid 13159587)
58. C.A. Rouzer, and B. Samuelsson The importance of hydroperoxide activation for the detection and assay of mammalian 5-lipoxygenase FEBS Lett 204 1986 293 296 (Pubitemid 17177117)
59. C. Feisst, C. Pergola, M. Rakonjac, A. Rossi, A. Koeberle, and G. Dodt Hyperforin is a novel type of 5-lipoxygenase inhibitor with high efficacy in vivo Cell Mol life Sci 66 2009 2759 2771
60. C.J. Smith, Y. Zhang, C.M. Koboldt, J. Muhammad, B.S. Zweifel, and A. Shaffer Pharmacological analysis of cyclooxygenase-1 in inflammation Proc Natl Acad Sci USA 95 1998 13313 13318 (Pubitemid 28509568)
61. P. Prasit, Z. Wang, C. Brideau, C.C. Chan, S. Charleson, and W. Cromlish The discovery of rofecoxib, [MK 966, Vioxx, 4-(4′-methylsulfonylphenyl)-3- phenyl-2(5H)-furanone], an orally active cyclooxygenase-2-inhibitor Bioorg Med Chem Lett 9 1999 1773 1778
62. B. Côté, L. Boulet, C. Brideau, D. Claveau, D. Ethier, and R. Frenette Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors Bioorg Med Chem Lett 17 2007 6816 6820 (Pubitemid 350061309)
63. A.T. Wecksler, V. Kenyon, N.K. Garcia, J.D. Deschamps, W.A. van der Donk, and T.R. Holman Kinetic and structural investigations of the allosteric site in human epithelial 15-lipoxygenase-2 Biochemistry 48 2009 8721 8730
64. I. Ivanov, D. Heydeck, K. Hofheinz, J. Roffeis, V.B. O'Donnell, and H. Kuhn Molecular enzymology of lipoxygenases Arch Biochem Biophys 503 2010 161 174
65. H. Safayhi, T. Mack, J. Sabieraj, M.I. Anazodo, L.R. Subramanian, and H.P. Ammon Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase J Pharmacol Exp Ther 261 1992 1143 1146
66. D. Albert, I. Zündorf, T. Dingermann, W.E. Müller, D. Steinhilber, and O. Werz Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase Biochem Pharmacol 64 2002 1767 1775 (Pubitemid 35355728)
67. E.R. Sailer, S. Schweizer, S.E. Boden, H.P. Ammon, and H. Safayhi Characterization of an acetyl-11-keto-beta-boswellic acid and arachidonate-binding regulatory site of 5-lipoxygenase using photoaffinity labeling FEBS J 256 1998 364 368 (Pubitemid 28404800)
68. C. Pergola, and O. Werz 5-Lipoxygenase inhibitors: a review of recent developments and patents Expert Opin Ther Pat 20 2010 355 375
69. A.W. Ford-Hutchinson, M. Gresser, and R.N. Young 5-Lipoxygenase Annu Rev Biochem 63 1994 383 417 (Pubitemid 24218638)
70. E. Bürkert, C. Arnold, T. Hammarberg, O. Rdmark, D. Steinhilber, and O. Werz The C2-like beta-barrel domain mediates the Ca2+-dependent resistance of 5-lipoxygenase activity against inhibition by glutathione peroxidase-1 J Biol Chem 278 2003 42846 42853 (Pubitemid 37351017)
71. S. Romanov, R. Wiesner, G. Myagkova, H. Kuhn, and I. Ivanov Affinity labeling of the rabbit 12/15-lipoxygenase using azido derivatives of arachidonic acid Biochemistry 45 2006 3554 3562
72. L. Fischer, D. Steinhilber, and O. Werz Molecular pharmacological profile of the nonredox-type 5-lipoxygenase inhibitor CJ-13,610 Br J Pharmacol 142 2004 861 868 (Pubitemid 39004096)
73. L. Fischer, D. Poeckel, E. Buerckert, D. Steinhilber, and O. Werz Inhibitors of actin polymerisation stimulate arachidonic acid release and 5-lipoxygenase activation by upregulation of Ca2+ mobilisation in polymorphonuclear leukocytes involving Src family kinases Biochim Biophys Acta 1736 2005 109 119 (Pubitemid 41262568)
74. G. Bain, C.D. King, M. Rewolinski, K. Schaab, A.M. Santini, and D. Shapiro Pharmacodynamics and pharmacokinetics of AM103, a novel inhibitor of 5-lipoxygenase-activating protein (FLAP) Clin Pharmacol Ther 87 2010 437 444
75. P. Rubin, and K.W. Mollison Pharmacotherapy of diseases mediated by 5-lipoxygenase pathway eicosanoids Prostaglandins Other Lipid Mediat 83 2007 188 197 (Pubitemid 46661257)
76. D.G. Tang, B. Bhatia, S. Tang, and R. Schneider-Broussard 15-Lipoxygenase 2 (15-LOX2) is a functional tumor suppressor that regulates human prostate epithelial cell differentiation, senescence, and growth (size) Prostaglandins Other Lipid Mediat 82 2007 135 146 (Pubitemid 44880169)
77. I. Cimen, E. Astarci, and S. Banerjee 15-Lipoxygenase-1 exerts its tumor suppressive role by inhibiting nuclear factor-kappa B via activation of PPAR gamma J Cell Biochem 112 2011 2490 2501
78. A.T. Baviskar, C. Madaan, R. Preet, P. Mohapatra, V. Jain, and A. Agarwal N-fused imidazoles as novel anticancer agents that inhibit catalytic activity of topoisomerase IIα and induce apoptosis in G1/S phase J Med Chem 54 2011 5013 5030