17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analogues

Journal of Medicinal Chemistry

Volumn 54, Issue 12, 2011, Pages 4109-4118

  Falck, John R ^a   Wallukat, Gerd ^b   Puli, Narender ^a   Goli, Mohan ^a   Arnold, Cosima ^b   Konkel, Anne ^b   Rothe, Michael ^c   Fischer, Robert ^d   Müller, Dominik N ^b   Schunck, Wolf Hagen ^b  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^c LIPIDOMIX GMBH   (Germany)

^d CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

17,18 EPOXYEICOSATETRAENOIC ACID; CALCIUM ION; ICOSAPENTAENOIC ACID; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTIARRHYTHMIC ACTIVITY; ARTICLE; CALCIUM TRANSPORT; CHRONOTROPISM; CONCENTRATION RESPONSE; ENANTIOMER; HEART MUSCLE CELL; MUSCLE FIBER CONTRACTION; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ALKENES; ANIMALS; ANIMALS, NEWBORN; ANTI-ARRHYTHMIA AGENTS; ARACHIDONIC ACIDS; BINDING SITES; CALCIUM; CELLS, CULTURED; EICOSAPENTAENOIC ACID; MYOCARDIAL CONTRACTION; MYOCYTES, CARDIAC; RATS; RATS, WISTAR; RECEPTORS, EICOSANOID; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79959434105     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm200132q     Document Type: Article

References (55)

1. Siddiqui, R. A.; Shaikh, S. R.; Sech, L. A.; Yount, H. R.; Stillwell, W.; Zaloga, G. P. Omega 3-fatty acids: health benefits and cellular mechanisms of action Mini-Rev. Med. Chem. 2004, 4, 859-871 (Pubitemid 39200073)
2. Geleijnse, J. M.; Giltay, E. J.; Schouten, E. G.; de Goede, J.; Oude Griep, L. M.; Teitsma-Jansen, A. M.; Katan, M. B.; Kromhout, D. Effect of low doses of Ω-3 fatty acids on cardiovascular diseases in 4,837 post-myocardial infarction patients: design and baseline characteristics of the Alpha Omega Trial Am. Heart J. 2010, 159, 539-546
3. Holub, B. J. Docosahexaenoic acid (DHA) and cardiovascular disease risk factors Prostaglandines, Leukotrienes Essent. Fatty Acids 2009, 81, 199-204
4. Lavie, C. J.; Milani, R. V.; Mehra, M. R.; Ventura, H. O. Omega-3 polyunsaturated fatty acids and cardiovascular diseases J. Am. Coll. Cardiol. 2009, 54, 585-594
5. Leaf, A.; Kang, J. X.; Xiao, Y.-F.; Billman, G. E. Clinical prevention of sudden cardiac death by n -3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by Ω-3 fish oils Circulation 2003, 107, 2646-2652 (Pubitemid 36667234)
6. von Schacky, C. Cardiovascular disease prevention and treatment Prostaglandins, Leukotrienes Essent. Fatty Acids 2009, 81, 193-198
7. Fedaĉko, J.; Pella, D.; Mechírová, V.; Horvath, P.; Rybár, R.; P. Varjassyová, P.; Vargová, V. Ω-3 PUFAs: from dietary supplements to medicines Pathophysiology 2007, 14, 127-132
8. Fischer, R.; Dechend, R.; Qadri, F.; Markovic, M.; Feldt, S.; Herse, F.; Park, J.-K.; Gapelyuk, A.; Schwarz, I.; Zacharzowsky, U. B.; Plehm, R.; Safak, E.; Heuser, A.; Schirdewan, A.; Luft, F. C.; Schunck, W.-H.; Muller, D. N. Dietary Ω-3 polyunsaturated fatty acids and direct renin inhibition improve electrical remodeling in a model of high human renin hypertension Hypertension 2008, 51, 540-546 (Pubitemid 351156445)
9. Marchioli, R.; Barzi, F.; Bomba, E.; Chieffo, C.; Di Gregorio, D.; Di Mascio, R.; Franzosi, M. G.; Geraci, E.; Levantesi, G.; Maggioni, A. P.; Mantini, L.; Marfisi, R. M.; Mastrogiuseppe, G.; Mininni, N.; Nicolosi, G. L.; Santini, M.; Schweiger, C.; Tavazzi, L.; Tognoni, G.; Tucci, C.; Valagussa, F. Early protection against sudden death by Ω-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nellInfarto Miocardico (GISSI)-Prevenzione Circulation 2002, 105, 1897-1903 (Pubitemid 34437615)
10. Harris, W. S. Omega-3 fatty acids and cardiovascular disease: a case for omega-3 index as a new risk factor Pharmacol. Res. 2007, 55, 217-223 (Pubitemid 46518155)
11. Pignier, C.; Revenaz, C.; Rauly-Lestienne, I.; Cussac, D.; Delhon, A.; Gardette, J.; Le Grand, B. Direct protective effects of poly-unsaturated fatty acids, DHA and EPA, against activation of cardiac late sodium current: a mechanism for ischemia selectivity Basic Res. Cardiol. 2007, 102, 553-564 (Pubitemid 47578400)
12. Oliw, E. H. 17 R (18 S)-Epoxyeicosatetraenoic acid, a cytochrome P-450 metabolite of 20:5Ω-3 in monkey seminal vesicles, is metabolized to novel prostaglandins Biochem. Biophys. Res. Commun. 1991, 178, 1444-1450
13. Smith, W. L. Cyclooxygenases, peroxide tone and the allure of fish oil Curr. Opin. Cell Biol. 2005, 17, 174-182 (Pubitemid 40380941)
14. Li, Y.; Kang, J. X.; Leaf, A. Differential effects of various eicosanoids on the production or prevention of arrhythmias in cultured neonatal rat cardiac myocytes Prostaglandins 1997, 54, 511-530 (Pubitemid 27444144)
15. 2α release from blood mononuclear leukocytes after oral supplementation of Ω-3 fatty acids: the OmegAD study J. Lipid Res. 2010, 51, 1179-1185
16. Schwarz, D.; Kisselev, P.; Chernogolov, A.; Schunck, W.-H.; Roots, I. Human CYP1A1 variants lead to differential eicosapentaenoic acid metabolite patterns Biochem. Biophys. Res. Commun. 2005, 336, 779-783 (Pubitemid 41338336)
17. Barbosa-Sicard, E.; Markovic, M.; Honeck, H.; Christ, B.; Muller, D. N.; Schunck, W.-H. Eicosapentaenoic acid metabolism by cytochrome P450 enzymes of the CYP2C subfamily Biochem. Biophys. Res. Commun. 2005, 329, 1275-1281 (Pubitemid 40568707)
18. Muller, D. N.; Schmidt, C.; Barbosa-Sicard, E.; Wellner, M.; Gross, V.; Hercule, H.; Markovic, M.; Honeck, H.; Luft, F. C.; Schunck, W. H. Mouse Cyp4a isoforms: enzymatic properties, gender- and strain-specific expression, and role in renal 20-hydroxyeicosatetraenoic acid formation Biochem. J. 2007, 403, 109-118 (Pubitemid 46569872)
19. Oliw, E. H.; Sprecher, H. W. Metabolism of polyunsaturated (Ω-3) fatty acids by monkey seminal vesicles: isolation and biosynthesis of omega-3 epoxides Biochim. Biophys. Acta 1991, 1086, 287-294
20. VanRollins, M. J. Epoxygenase metabolites of docosahexaenoic and eicosapentaenoic acids inhibit platelet aggregation at concentrations below those affecting thromboxane synthesis Pharmacol. Exp. Ther. 1995, 274, 798-804
21. Fer, M.; Dreano, Y.; Lucas, D.; Corcos, L.; Salauen, J.-P.; Berthou, F.; Amet, Y. Metabolism of eicosapentaenoic and docosahexaenoic acids by recombinant human cytochromes P450 Arch. Biochem. Biophys. 2008, 471, 116-125
22. Schwarz, D.; Kisselev, P.; Ericksen, S. S.; Szklarz, G. D.; Chernogolov, A.; Honeck, H.; Schunck, W.-H.; Roots, I. Arachidonic and eicosapentaenoic acid metabolism by human CYP1A1: highly stereoselective formation of 17(R),18(S)-epoxyeicosatetraenoic acid Biochem. Pharmacol. 2004, 67, 1445-1457 (Pubitemid 38388207)
23. Lucas, D.; Goulitquer, S.; Marienhagen, J.; Fer, M.; Dreano, Y.; Schwaneberg, U.; Amet, Y.; Corcos, L. Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450 J. Lipid Res. 2010, 51, 1125-1133
24. Arnold, C.; Markovic, M.; Blossey, K.; Wallukat, G.; Fischer, R.; Dechend, R.; Konkel, A.; von Schacky, C.; Luft, F. C.; Muller, D. N.; Rothe, M.; Schunck, W. H. Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of omega-3 fatty acids J. Biol. Chem. 2010, 285, 32720-32733
25. Knapp, H. R.; Miller, A. J.; Lawson, J. A. Urinary excretion of diols derived from eicosapentaenoic acid during n-3 fatty acid ingestion by man Prostaglandins 1991, 42, 47-54
26. Shearer, G. C.; Harris, W. S.; Pedersen, T. L.; Newman, J. W. Detection of omega-3 oxylipins in human plasma and response to treatment with omega-3 acid ethyl esters J. Lipid Res. 2009, 51, 2074-2081
27. Lauterbach, B.; Barbosa-Sicard, E.; Wang, M. H.; Honeck, H.; Kärgel, E.; Theuer, J.; Schwartzman, M. L.; Haller, H.; Luft, F. C.; Gollasch, M.; Schunck, W.-H. Cytochrome P450-dependent eicosapentaenoic acid metabolites are novel BK channel activators Hypertension 2002, 39, 609-613 (Pubitemid 34165192)
28. Hercule, H. C.; Salanova, B.; Essin, K.; Honeck, H.; Falck, J. R.; Sausbier, M.; Ruth, P.; Schunck, W.-H.; Luft, F. C.; Gollasch, M. The vasodilator 17,18-epoxyeicosatetraenoic acid targets the pore-forming BK alpha channel subunit in rodents Exp. Physiol. 2007, 92, 1067-1076 (Pubitemid 47568840)
29. Gauthier, K. M.; Deeter, C.; Krishna, U. M.; Reddy, Y. K.; Bondlela, M.; Falck, J. R.; Campbell, W. B. 14,15-Epoxyeicosa-5(Z)-enoic acid: a selective epoxyeicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries Circ. Res. 2002, 90, 1028-1036 (Pubitemid 34633870)
30. 125I-14,15- epoxyeicosa-8(Z)-enoic acid J. Pharmacol. Exp. Ther. 2008, 324, 1019-1027 (Pubitemid 351397827)
31. Morin, C.; Sirois, M.; Echave, V.; Rizcallah, E.; Rousseau, E. Relaxing effects of 17(18)-EpETE on arterial and airway smooth muscles in human lung Am. J. Physiol.: Lung Cell. Mol. Physiol. 2009, 296, L130-139
32. Morin, C.; Sirois, M.; Echave, V.; Albadine, R.; Rousseau, E. 17,18-EpETE targets PPAR{gamma} and p38MAPK to mediate its anti-inflammatory effect in lung: role of sEH Am. J. Respir. Cell Mol. Biol. 2009, 43, 564-575
33. Recent review: Spector, A. A.; Norris, A. W. Action of epoxyeicosatrienoic acids on cellular function Am. J. Physiol.: Cell Physiol. 2007, 292, C996-1012
34. 125I-14,15- epoxyeicosa-8(Z)-enoic acid J. Pharmacol. Exp. Ther. 2008, 324, 1019-1027 (Pubitemid 351397827)
35. 125Iodo-14,15-epoxyeicosa-5(Z)-enoic acid: a high-affinity radioligand used to characterize the epoxyeicosatrienoic acid antagonist binding site J. Pharmacol. Exp. Ther. 2009, 331, 1137-1145
36. Kang, J. X.; Leaf, A. Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 9886-9890 (Pubitemid 24311913)
37. Kang, J. X.; Leaf, A. Prevention and termination of β-adrenergic agonist-induced arrhythmias by free polyunsaturated fatty acids in neonatal rat cardiac myocytes Biochem. Biophys. Res. Commun. 1995, 208, 629-636
38. Kang, J. X.; Xiao, Y. F.; Leaf, A. Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 3997-4001
39. In the context of this antiarrhythmic study, agonist activity refers to the ability of a species to reduce the compound-induced abnormal or pathogenic beating rate of NRCMs towards the normal, spontaneous beating rate of 120-150 beats/min. Inverse agonist activity refers to the ability of a species to increase the beating rate beyond the normal, spontaneous beating rate; i.e., it has a biological activity opposite to that of an agonist. An antagonist is a species capable of partially or completely blocking the activity of an agonist or inverse agonist while having no significant effect of its own on receptor or physiological activity.
40. Review: Dobrev, D.; Nattel, S. New antiarrhythmic drugs for treatment of atrial fibrillation Lancet 2010, 375, 1212-1223
41. For a discussion of chemical and metabolic restrictions for epoxanoids, see the following: Falck, J. R.; Kodela, R.; Manne, R.; Atcha, K. R.; Puli, N.; Dubasi, N.; Manthati, V. L.; Capdevila, J. H.; Yi, X.-Y.; Goldman, D. H.; Morisseau, C.; Hammock, B. D.; Campbell, W. B. 14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) surrogates containing epoxide bioisosteres: influence upon vascular relaxation and soluble epoxide hydrolase inhibition J. Med. Chem. 2009, 52, 5069-5075
42. To estimate comparative metabolic stability, EPA epoxide 1 and several analogues were incubated for 30 min at 37 °C with rat liver homogenate in the presence of NADPH and analyzed by LC/MS (Supporting Information).
43. Cowart, L. A.; Wei, S.; Hsu, M.-H.; Johnson, E. F.; Krishna, M. U.; Falck, J. R.; Capdevila, J. H. The CYP4A isoforms hydroxylate epoxyeicosatrienoic acids to form high affinity peroxisome proliferator- activated receptor ligands J. Biol. Chem. 2002, 277, 35105-35112
44. Imig, J. D. Cardiovascular therapeutic aspects of soluble epoxide hydrolase inhibitors Cardiovasc. Drug Rev. 2006, 24, 169-188 (Pubitemid 46696923)
45. Morisseau, C.; Goodrow, M. H.; Dowdy, D.; Zheng, J.; Greene, J. F.; Sanborn, J. R.; Hammock, B. D. Potent urea and carbamate inhibitors of soluble epoxide hydrolases Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 8849-8854 (Pubitemid 29374671)
46. Kowalski, J. A.; Swinamer, A. D.; Muegge, I.; Eldrup, A. B.; Kukulka, A.; Cywin, C. L.; De Lombaert, S. Rapid synthesis of an array of trisubstituted urea-based soluble epoxide hydrolase inhibitors facilitated by a novel solid-phase method Bioorg. Med. Chem. Lett. 2010, 20, 3703-3707
47. Shen, H. C.; Ding, F.-X.; Wang, S.; Deng, Q.; Zhang, X.; Chen, Y.; Zhou, G.; Xu, S.; Chen, H.-s.; Tong, X.; Tong, V.; Mitra, K.; Kumar, S.; Tsai, C.; Stevenson, A. S.; Pai, L.-Y.; Alonso-Galicia, M.; Chen, X.; Soisson, S. M.; Roy, S.; Zhang, B.; Tata, J. R.; Berger, J. P.; Colletti, S. L. Discovery of a highly potent, selective, and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagement J. Med. Chem. 2009, 52, 5009-5012
48. Gunstone, F. D.; Lie Ken Jie, M. Fatty acids. 24. Synthesis of ten octadecadiynoic acids and of the related cis,cis- and trans,trans- octadecadienoic acids Chem. Phys. Lipids 1970, 4, 1-14
49. 3-iodane and carbon tetrachloride Tetrahedron Lett. 2004, 45, 3557-3559 (Pubitemid 38481725)
50. Seifert, R. M. Synthesis, spectra, odor properties, and structural relationship of (Z)-6-nonenal and (Z)-5-octen-1-ol to fruit fly attractants J. Agric. Food Chem. 1981, 29, 647-649
51. Harcken, C.; Bruckner, R. Elucidation of the stereostructure of the annonaceous acetogenin (+)-montecristin through total synthesis New J. Chem. 2001, 25, 40-54 (Pubitemid 32164798)
52. Wessel, J. C.; Matyja, M.; Neugebauer, M.; Kiefer, H.; Daldrup, T.; Tarbah, F. A.; Weber, H. Characterization of oxalic acid derivatives as new metabolites of metamizol (dipyrone) in incubated hens egg and human Eur. J. Pharm. Sci. 2006, 28, 15-25
53. Molander, G. A.; Figueroa, R. cis -Dihydroxylation of unsaturated potassium alkyl- and aryltrifluoroborates Org. Lett. 2006, 8, 75-78 (Pubitemid 43112841)
54. Corey, E. J.; Eckrich, T. M. A method for the stereospecific synthesis of chiral cis -2-alkylcyclopropyllithium reagents Tetrahedron Lett. 1984, 25, 2415-2418
55. Wallukat, G.; Munioz Saravia, S. G.; Haberland, A.; Bartel, S.; Araujo, R.; Valda, G.; Duchen, D.; Diaz Ramirez, I.; Borges, A. C.; Schimke, I. Distinct patterns of autoantibodies against G-protein-coupled receptors in Chagas cardiomyopathy and megacolon: their potential impact for early risk assessment in asymptomatic Chagas patients J. Am. Coll. Cardiol. 2010, 55, 463-468