Modulation of leukotriene pathway – potential targets
Authors:
Peter Hoffman; Lýdia Bezáková
Authors place of work:
Univerzita Komenského v Bratislave, Farmaceutická fakulta, Katedra bunkovej a molekulárnej biológie liečiv
Published in the journal:
Čes. slov. Farm., 2012; 61, 101-106
Category:
Přehledy a odborná sdělení
Summary
Leukotrienes (LT), namely cysteinyl LT and LTB4, are potent lipid mediators taking part in the signal pathways of many inflammatory processes. The arachidonic acid transformation into leukotrienes can be signed as the leukotriene pathway. The key enzyme is 5-lipoxygenase, a dioxygenase containing a nonheme-bound ferric central ion, which in the catalytic complex with 5-lipoxygenase activating protein forms 5-hydroperoxyeicosatetraenoic acid. In the next steps this process involves leukotriene A4-hydrolase or leukotriene C4-synthase. According to the progress in recent years in the area of X-ray structural analysis and revealed 3D structure of these biocatalysts, especially their active sites, the development of new drugs markedly accelerated. This complicated enzymatically controlled process offers several possibilities of modulation and presents new approaches to the treatment of typical inflammatory diseases as well as in the therapy of atherosclerosis and cancer.
Keywords:
leukotrienes, 5-lipoxygenase, modulation, leukotriene pathway
Zdroje
1. Steinhilber, D., Fischer, A. S., Metzner, J., Steinbrink, S. D., Roos, J., Ruthardt, M., Maier, T. J.: 5-lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumorigenesis. Front Pharmacol. 2010; 1, doi: 10.3389//fphar.2010.00143
2. Folco G., Murphy R. C.: Eicosanoid transcellular biosynthesis: from cell-cell interactions to in vivo tissue responses. Pharmacol Rev 2006; 58, 1–14.
3. Sala A., Bolla M., Zarini S., Muller-Peddinghaus R., Folco G.: Release of leukotriene A4 versus leukotriene B4 from human polymorphonuclear leukocytes. J Biol Chem 1996; 271, 17944–17948.
4. McGee J. E., Fitzpatrick , F. A.: Erythrocyte-neutrophil interactions: formation of leukotriene B4 by transcellular biosynthesis. Proc Natl Acad Sci, 1986; 83, 1349–1353.
5. Maclouf J. A., Murphy R. C.: Transcellular metabolism of neutrophil-derived leukotriene A4 by human platelets: a potential cellular source of leukotriene C4. J Biol Chem, 1988; 263, 174–181.
6. Grimminger F., Sibelius U., Seeger W.: Amplification of LTB4 generation in AM–PMN cocultures: transcellular 5-lipoxygenase metabolism. Am J Physiol, 1991; 261, L195– L203.
7. Montuschi P., Sala A., Dahlén S. E., Folco G.: Pharmacological modulation of the leukotriene pathway in allergic airway disease. Drug Discov Today, 2007; 12, 404–412.
8. Kamohara M., Takasaki J., Matsumoto M., Matsumoto S. I., Saito T., Soga T., Matsushime H., Furuichi K.: Functional characterization of cysteinyl leukotriene CysLT2 receptor on human coronary artery smooth muscle cells. Biochem Biophys Res Commun, 2001; 287, 1088–1092.
9. Toda A., Yokomizo T., Shimizu T.: Leukotriene B4 receptors. Prostag Oth Lipid M, 2002; 68-69, 575–585.
10. Yokomizo T., Kato K., Hagiya H, Izumi T, Shimizu T.: A pilot study examining the role of zileuton in atopic dermatitis. Ann Allergy Asthma Immunol, 1997; 83, 620–624.
11. Bäck M., Bu D. X., Bränström R. Sheikine Y., Yan Z. Q., Hansson G. K.: Leukotriene B4 signaling through NF-kappaB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia. Proc Natl Acad Sci USA, 2005; 102, 17501-17506.
12. Werz O., Steinhilber D.: Therapeutic options for 5–lipoxygenase inhibitors. Pharmacol Therapeut, 2006; 112, 701–718.
13. Khanapure S. P., Garvey D. S., Janero D. R., Letts L. G.: Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Curr Top Med Chem, 2007; 7, 311–340.
14. Gillard J., Ford-Hutchinson A. W., Chan C., Charleson S., Denis D., Foster A., Fortin R., Leger S., McFarlane C. S., Morton H. et al.: 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, 1989; 67, 456–464.
15. Radmark O., Samuelsson B.: Regulation of the activity of 5–lipoxygenase, a key enzyme in leukotriene biosynthesis. Biochem Biophys Res Commun, 2010; 396, 105–110.
16. Bäck, M.: Inhibitors of the 5–lipoxygenase pathway in atherosclerosis. Curr Pharm Design, 2009; 15, 3116–3132.
17. Zaitsu M., Hamasaki Y., Matsuo M., Kukita A., Tsuji K., Miyazaki M., Hayasaki R., Muro E., Yamamoto S., Kobayashi I., Ichimaru T., Kohashi O., Miyazaki S.: New induction of leukotriene A4 hydrolase by interleukin-4 and interleukin–13 in human polymorphonuclear leukocytes. Blood, 2000; 96, 601–609.
18. Sampson A. P.: Leukotriene C4 synthase: the engine of aspirin intolerance? Clin Exp Allergy, 2011; 41, 1050–1053.
19. Young R. N.: Inhibitors of 5-lipoxygenase: a therapeutic potencial yet to be fully realized? Eur J Med Chem, 1999; 34, 671–685.
20. Bruneau P., Delvare C., Edwards M. P., McMillan R. M.: Indazolines, a new series of redox-active 5-lipoxygenase inhibitors with built-in selectivity and oral activity. J Med Chem, 1991; 34, 1028–1036.
21. Black A. K., Camp R. D. R., Derm F. F., Mallet A. I., Cunningham F. M., Hofbauer M., Greaves M. W.: Pharmacologic and clinical effects of lonapalene (RS-43179), a 5-lipoxygenase inhibitor, in psoriasis. J Invest Dermatol, 1990; 95, 50–54.
22. Liu M. C., Dube L. M., Lancaster J.: Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. J Allergy Clin Immunol, 1996; 98, 859–871.
23. Tardif J. C., L’Allier P. L., Ibrahim R., Gregoire J. C., Nozza A., Cossette M., Kouz S., Lavoie M. A., Paquin J., Brotz T. M., Taub R., Pressacco J.: Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome. Circulation, 2010; 3, 298–307.
24. Sampson A. P.: FLAP inhibitors for treatment of inflammatory diseases. Curr Opin Investig Drugs, 2009; 10, 1163–1172.
25. Hakonarson H., Thorvaldsson S., Helgadottir A., Gudbjartsson D., Zink F., Andresdottir M. et al.: Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA, 2005; 293, 2245–2256.
26. Bain G., King C. D., Rewolinski M., Schaab K., Santini A. M., Shapiro D., Moran M., Rooij S. W., Roffel A. F., Schulenga-Hut P., Milne G. L. et al.: Pharmacodynamics and pharmacokinetics of AM103, a novel inhibitor of 5-lipoxygenase-activating protein (FLAP). Clin Pharmacol Ther, 2010; 87, 437–444.
27. Penning T. D.: Inhibitors of leukotriene A4 (LTA4) hydrolase as potential anti-inflammatory agents. Curr Pharm Design, 2001; 7, 163–179.
28. Sandanayaka V., Mamat B., Bhagat N., Bedell L., Halldorsdottir G., Sigthorsdottir H., Andrésson P., Kiselyov A., Gurney M., Singh J.: Discovery of novel leukotriene A4 hydrolase inhibitors based on piperidine and piperazine scaffolds. Bioorg Med Chem Lett, 20, 2010; 20, 2851–2854.
29. Diaz-Gonzalez F., Alten R. H. E., Bensen W. G., Bown J. P., Sibley J. T., Dougados M., Bombardieri S., Durez P., Ortiz P., de-Miquel G., Staab A. et al.: Clinical trial of a leukotriene B4 receptor antagonist, BIIL 284, in patients with rheumatoid arthritis. Ann Rheum Dis, 2007; 66, 628–632.
30. Alten R., Gromnica-Ihle E., Pohl C., Emmerich J., Steffgen J., Roscher R., Sigmund R., Schmolke B., Steinmann G.: Inhibition of leukotriene B4-induced CD11B/CD18 (Mac–1) expression by BIIL 284, a new long acting LTB4 receptor antagonist, in patients with rheumatoid arthritis. Ann Rheum Dis, 2004; 63, 170–176.
31. Hicks A., Monkarsh S. P., Hoffman A. F., Goodnow R. Jr.: Leukotriene B4 receptor antagonists as therapeutics for inflammatory disease: preclinical and clinical developments. Expert Opin Investig Drugs, 2007; 16, 1909–1920.
32. Saif M. W., Oettle H., Vervenne W. L., Thomas J. P., Spitzer G., Visseren–Grul C., Enas N., Richards D. A.: Randomized double-blind phase II trial comparing gemcitabine plus LY293111 versus gemcitabine plus placebo in advanced adenocarcinoma of the pancreas. Cancer J, 2009; 15, 339–343.
33. Augstein J., Farmer J. B., Lee T. B., Sheard P., Tattersall M. L.: Selective inhibitor of slow reacting substrate of anaphylaxis. Nat New Biol, 1973; 245, 215–217.
34. Charlier C., Michaux C.: Dual inhzibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur J Med Chem, 2003; 38, 645–659.
35. Furberg C. D., Psaty B. M., Fitzgerald G. A.: Parecoxib, valdecoxib, and cardiovascular risk. Circulation, 2005; 111, 249.
36. Bannwarth B.: Is licofelone, a dual inhibitor of cyclo-oxygenase and 5-lipoxygenase, a promising alternative in anti-inflammatory therapy? Fund Clin Pharmacol, 2004; 18, 125–130.
37. Peng J., van Loon J. J. A., Zheng S., Dicke M.: Herbivore-induced volatiles of cabbage (Brassica oleracea) prime defence in neighbouring intact plants. Plant Biol, 2011; 13, 276–284.
38. Raynauld J. P., Martel-Pelletier J., Bias P., Laufer S., Haraoui B., Choquette D., Bealieu A. D., Abram F., Dorais M., Vignon E., Pelletier J. P.: Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI. Ann Rheum Dis, 2009; 68, 938–947.
39. Rotondo S., Dell’Elba G., Krauze-Brzósko K., Manarini S., Martelli N., Pecce R., Evangelista V., Cerletti C.: Licofelone, a dual lipoxygenase-cyclooxygenase inhibitor, downregulates polymorphonuclear leukocyte and platelet function. Eur J Pharmacol, 2002; 453, 131–139.
Štítky
Farmácia FarmakológiaČlánok vyšiel v časopise
Česká a slovenská farmacie
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2012 Číslo 3
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