SAR studies on curcumin's pro-inflammatory targets: Discovery of prenylated pyrazolocurcuminoids as potent and selective novel inhibitors of 5-lipoxygenase

Journal of Medicinal Chemistry

Volumn 57, Issue 13, 2014, Pages 5638-5648

  Koeberle, Andreas ^a   Muñoz, Eduardo ^b   Appendino, Giovanni B ^c   Minassi, Alberto ^c   Pace, Simona ^a,d   Rossi, Antonietta ^d   Weinigel, Christina ^e   Barz, Dagmar ^e   Sautebin, Lidia ^d   Caprioglio, Diego ^c   Collado, Juan A ^b   Werz, Oliver ^a  

^a FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

^b UNIVERSITY OF CÓRDOBA   (Spain)

^c UNIVERSITY OF EASTERN PIEDMONT   (Italy)

^d UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^e JENA UNIVERSITY HOSPITAL   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1,5 BIS(3 FLUORO 4 HYDROXY 5 METHOXYPHENYL)PENTA 1,4 DIEN 3 ONE; 3 [3 TERT BUTYLTHIO 1 (4 CHLOROBENZYL) 5 ISOPROPYL 2 INDOLYL] 2,2 DIMETHYLPROPIONIC ACID; 4,4',2,2' (1H PYRAZOLE 3,5 DIYL)BIS(ETHENE 2,1 DIYL)BIS[2 METHOXY 6 (3 METHYLBUT 2 ENYL)PHENOL]; 5,5' DIFLUOROCURCUMIN; ARACHIDONATE 12 LIPOXYGENASE; ARACHIDONATE 15 LIPOXYGENASE; ARACHIDONATE 5 LIPOXYGENASE; CURCUMIN; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDOMETACIN; LIPOXYGENASE INHIBITOR; PROSTAGLANDIN E SYNTHASE; STAT3 PROTEIN; TRANSCRIPTION FACTOR NRF2; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BLOOD; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; DRUG TARGETING; ENZYME INHIBITION; HUMAN; HUMAN CELL; HYDROGENATION; MALE; MONOCYTE; MOUSE; NONHUMAN; PERITONITIS; PRENYLATION; STRUCTURE ACTIVITY RELATION; THROMBOCYTE;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ARACHIDONATE 5-LIPOXYGENASE; CURCUMIN; HUMANS; LIPOXYGENASE INHIBITORS; MALE; MICE; MONOCYTES; PERITONITIS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84904288914     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500308c     Document Type: Article

References (56)

1. Gupta, S. C.; Kismali, G.; Aggarwal, B. B. Curcumin, a component of turmeric: from farm to pharmacy BioFactors 2013, 39, 2-13
2. Hatcher, H.; Planalp, R.; Cho, J.; Torti, F. M.; Torti, S. V. Curcumin: from ancient medicine to current clinical trials Cell. Mol. Life Sci. 2008, 65, 1631-1652
3. Cuomo, J.; Appendino, G.; Dern, A. S.; Schneider, E.; McKinnon, T. P.; Brown, M. J.; Togni, S.; Dixon, B. M. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation J. Nat. Prod. 2011, 74, 664-669
4. Balogun, E.; Hoque, M.; Gong, P.; Killeen, E.; Green, C. J.; Foresti, R.; Alam, J.; Motterlini, R. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element Biochem. J. 2003, 371, 887-895 (Pubitemid 36578887)
5. Singh, S.; Aggarwal, B. B. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected] J. Biol. Chem. 1995, 270, 24995-25000
6. Choudhuri, T.; Pal, S.; Agwarwal, M. L.; Das, T.; Sa, G. Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction FEBS Lett. 2002, 512, 334-340 (Pubitemid 34164505)
7. Natarajan, C.; Bright, J. J. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes J. Immunol. 2002, 168, 6506-6513 (Pubitemid 34620077)
8. Balasubramanyam, K.; Varier, R. A.; Altaf, M.; Swaminathan, V.; Siddappa, N. B.; Ranga, U.; Kundu, T. K. Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription J. Biol. Chem. 2004, 279, 51163-51171 (Pubitemid 40017859)
9. Hong, J.; Bose, M.; Ju, J.; Ryu, J. H.; Chen, X.; Sang, S.; Lee, M. J.; Yang, C. S. Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase Carcinogenesis 2004, 25, 1671-1679 (Pubitemid 39214309)
10. Handler, N.; Jaeger, W.; Puschacher, H.; Leisser, K.; Erker, T. Synthesis of novel curcumin analogues and their evaluation as selective cyclooxygenase-1 (COX-1) inhibitors Chem. Pharm. Bull. 2007, 55, 64-71 (Pubitemid 46067584)
11. Hasmeda, M.; Polya, G. M. Inhibition of cyclic AMP-dependent protein kinase by curcumin Phytochemistry 1996, 42, 599-605 (Pubitemid 27096848)
12. Mancuso, C.; Barone, E. Curcumin in clinical practice: myth or reality? Trends Pharmacol. Sci. 2009, 30, 333-334
13. Koeberle, A.; Northoff, H.; Werz, O. Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1 Mol. Cancer Ther. 2009, 8, 2348-2355
14. Schiborr, C.; Kocher, A.; Behnam, D.; Jandasek, J.; Toelstede, S.; Frank, J. The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes Mol. Nutr. Food Res. 2014, 58, 516-527
15. Esatbeyoglu, T.; Huebbe, P.; Ernst, I. M.; Chin, D.; Wagner, A. E.; Rimbach, G. Curcumin-from molecule to biological function Angew. Chem., Int. Ed. Engl. 2012, 51, 5308-5332
16. Li, R.; Qiao, X.; Li, Q.; He, R.; Ye, M.; Xiang, C.; Lin, X.; Guo, D. Metabolic and pharmacokinetic studies of curcumin, demethoxycurcumin and bisdemethoxycurcumin in mice tumor after intragastric administration of nanoparticle formulations by liquid chromatography coupled with tandem mass spectrometry J. Chromatogr., B: Anal. Technol. Biomed. Life Sci. 2011, 879, 2751-2758
17. Koeberle, A.; Werz, O. Inhibitors of the microsomal prostaglandin E(2) synthase-1 as alternative to non steroidal anti-inflammatory drugs (NSAIDs)-a critical review Curr. Med. Chem. 2009, 16, 4274-4296
18. Werz, O.; Steinhilber, D. Therapeutic options for 5-lipoxygenase inhibitors Pharmacol. Ther. 2006, 112, 701-718 (Pubitemid 44592614)
19. Peters-Golden, M.; Henderson, W. R., Jr. Leukotrienes N. Engl. J. Med. 2007, 357, 1841-1854
20. Back, M.; Dahlen, S. E.; Drazen, J. M.; Evans, J. F.; Serhan, C. N.; Shimizu, T.; Yokomizo, T.; Rovati, G. E. International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene receptor nomenclature, distribution, and pathophysiological functions Pharmacol. Rev. 2011, 63, 539-584
21. Agrawal, D. K.; Mishra, P. K. Curcumin and its analogues: potential anticancer agents Med. Res. Rev. 2010, 30, 818-860
22. Ahmad, W.; Kumolosasi, E.; Jantan, I.; Bukhari, S. N.; Jasamai, M. Effects of novel diarylpentanoid analogues of curcumin on secretory phospholipase A, cyclooxygenases, lipoxygenase and microsomal prostaglandin E synthase-1 Chem. Biol. Drug Des. 2014, 83, 670-681
23. Flynn, D. L.; Belliotti, T. R.; Boctor, A. M.; Connor, D. T.; Kostlan, C. R.; Nies, D. E.; Ortwine, D. F.; Schrier, D. J.; Sircar, J. C. Styrylpyrazoles, styrylisoxazoles, and styrylisothiazoles. Novel 5-lipoxygenase and cyclooxygenase inhibitors J. Med. Chem. 1991, 34, 518-525
24. Jankun, J.; Aleem, A. M.; Malgorzewicz, S.; Szkudlarek, M.; Zavodszky, M. I.; Dewitt, D. L.; Feig, M.; Selman, S. H.; Skrzypczak-Jankun, E. Synthetic curcuminoids modulate the arachidonic acid metabolism of human platelet 12-lipoxygenase and reduce sprout formation of human endothelial cells Mol. Cancer Ther. 2006, 5, 1371-1382 (Pubitemid 43881331)
25. Gafner, S.; Lee, S. K.; Cuendet, M.; Barthelemy, S.; Vergnes, L.; Labidalle, S.; Mehta, R. G.; Boone, C. W.; Pezzuto, J. M. Biologic evaluation of curcumin and structural derivatives in cancer chemoprevention model systems Phytochemistry 2004, 65, 2849-2859 (Pubitemid 40292116)
26. Weber, W. M.; Hunsaker, L. A.; Gonzales, A. M.; Heynekamp, J. J.; Orlando, R. A.; Deck, L. M.; Vander Jagt, D. L. TPA-induced up-regulation of activator protein-1 can be inhibited or enhanced by analogs of the natural product curcumin Biochem. Pharmacol. 2006, 72, 928-940 (Pubitemid 44374461)
27. Clark, M. T.; Miller, D. D. New syntheses of 2-fluoroisovanillin and 5-fluorovanillin J. Org. Chem. 1986, 51, 4072-4073 (Pubitemid 17202219)
28. Pabon, H. J. J. A synthesis of curcumin and related compounds Recl. Trav. Chim. Pays-Bas 1964, 83, 379-386
29. Minassi, A.; Sanchez-Duffhues, G.; Collado, J. A.; Munoz, E.; Appendino, G. Dissecting the pharmacophore of curcumin. Which structural element is critical for which action? J. Nat. Prod. 2013, 76, 1105-1112
30. Narlawar, R.; Pickhardt, M.; Leuchtenberger, S.; Baumann, K.; Krause, S.; Dyrks, T.; Weggen, S.; Mandelkow, E.; Schmidt, B. Curcumin-derived pyrazoles and isoxazoles: Swiss army knives or blunt tools for Alzheimer's disease? ChemMedChem 2008, 3, 165-172
31. Muller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals: looking beyond intuition Science 2007, 317, 1881-1886 (Pubitemid 47509426)
32. Botta, B.; Menendez, P.; Zappia, G.; de Lima, R. A.; Torge, R.; Monachea, G. D. Prenylated isoflavonoids: botanical distribution, structures, biological activities and biotechnological studies. An update (1995-2006) Curr. Med. Chem. 2009, 16, 3414-3468
33. Bernabe-Pineda, M.; Ramirez-Silva, M. T.; Romero-Romo, M.; Gonzalez-Vergara, E.; Rojas-Hernandez, A. Determination of acidity constants of curcumin in aqueous solution and apparent rate constant of its decomposition Spectrochim. Acta, Part A 2004, 60, 1091-1097
34. Lv, H.; She, G. Naturally occurring diarylheptanoids Nat. Prod. Commun. 2010, 5, 1687-1708
35. Botta, B.; Vitali, A.; Menendez, P.; Misiti, D.; Delle Monache, G. Prenylated flavonoids: pharmacology and biotechnology Curr. Med. Chem. 2005, 12, 717-739
36. Werz, O. Inhibition of 5-lipoxygenase product synthesis by natural compounds of plant origin Planta Med. 2007, 73, 1331-1357 (Pubitemid 350084452)
37. Koeberle, A.; Pollastro, F.; Northoff, H.; Werz, O. Myrtucommulone, a natural acylphloroglucinol, inhibits microsomal prostaglandin E2 synthase-1 Br. J. Pharmacol. 2009, 156, 952-961
38. Bauer, J.; Koeberle, A.; Dehm, F.; Pollastro, F.; Appendino, G.; Northoff, H.; Rossi, A.; Sautebin, L.; Werz, O. Arzanol, a prenylated heterodimeric phloroglucinyl pyrone, inhibits eicosanoid biosynthesis and exhibits anti-inflammatory efficacy in vivo Biochem. Pharmacol. 2011, 81, 259-268
39. Koeberle, A.; Rossi, A.; Bauer, J.; Dehm, F.; Verotta, L.; Northoff, H.; Sautebin, L.; Werz, O. Hyperforin, an anti-inflammatory constituent from St. John's wort, inhibits microsomal prostaglandin E(2) synthase-1 and suppresses prostaglandin E(2) formation Front. Pharmacol. 2011, 2, 7
40. Koeberle, A.; Northoff, H.; Werz, O. Identification of 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 as functional targets of the anti-inflammatory and anti-carcinogenic garcinol Biochem. Pharmacol. 2009, 77, 1513-1521
41. Tateson, J. E.; Randall, R. W.; Reynolds, C. H.; Jackson, W. P.; Bhattacherjee, P.; Salmon, J. A.; Garland, L. G. Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids: biochemical assessment in vitro and ex vivo Br. J. Pharmacol. 1988, 94, 528-539
42. Cote, B.; Boulet, L.; Brideau, C.; Claveau, D.; Ethier, D.; Frenette, R.; Gagnon, M.; Giroux, A.; Guay, J.; Guiral, S.; Mancini, J.; Martins, E.; Masse, F.; Methot, N.; Riendeau, D.; Rubin, J.; Xu, D.; Yu, H.; Ducharme, Y.; Friesen, R. W. Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors Bioorg. Med. Chem. Lett. 2007, 17, 6816-6820 (Pubitemid 350061309)
43. Wang, Y. J.; Pan, M. H.; Cheng, A. L.; Lin, L. I.; Ho, Y. S.; Hsieh, C. Y.; Lin, J. K. Stability of curcumin in buffer solutions and characterization of its degradation products J. Pharm. Biomed. Anal. 1997, 15, 1867-1876
44. Sporn, M. B.; Liby, K. T. NRF2 and cancer: the good, the bad and the importance of context Nature Rev. Cancer 2012, 12, 564-571
45. Funk, C. D. Prostaglandins and leukotrienes: advances in eicosanoid biology Science 2001, 294, 1871-1875 (Pubitemid 33101574)
46. Hanke, T.; Dehm, F.; Liening, S.; Popella, S. D.; Maczewsky, J.; Pillong, M.; Kunze, J.; Weinigel, C.; Barz, D.; Kaiser, A.; Wurglics, M.; Lammerhofer, M.; Schneider, G.; Sautebin, L.; Schubert-Zsilavecz, M.; Werz, O. Aminothiazole-featured pirinixic acid derivatives as dual 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 inhibitors with improved potency and efficiency in vivo J. Med. Chem. 2013, 56, 9031-9044
47. Rao, T. S.; Currie, J. L.; Shaffer, A. F.; Isakson, P. C. In vivo characterization of zymosan-induced mouse peritoneal inflammation J. Pharmacol. Exp. Ther. 1994, 269, 917-925 (Pubitemid 24204169)
48. Gillard, J.; Ford-Hutchinson, A. W.; Chan, C.; Charleson, S.; Denis, D.; Foster, A.; Fortin, R.; Leger, S.; McFarlane, C. S.; Morton, H. 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 (Pubitemid 19186702)
49. Ringman, J. M.; Frautschy, S. A.; Teng, E.; Begum, A. N.; Bardens, J.; Beigi, M.; Gylys, K. H.; Badmaev, V.; Heath, D. D.; Apostolova, L. G.; Porter, V.; Vanek, Z.; Marshall, G. A.; Hellemann, G.; Sugar, C.; Masterman, D. L.; Montine, T. J.; Cummings, J. L.; Cole, G. M. Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study Alzheimer's Res. Ther. 2012, 4, 43
50. Caldarelli, A.; Penucchini, E.; Caprioglio, D.; Genazzani, A. A.; Minassi, A. Synthesis and tubulin-binding properties of non-symmetrical click C5-curcuminoids Bioorg. Med. Chem. 2013, 21, 5510-5517
51. Albert, D.; Zundorf, I.; Dingermann, T.; Muller, W. E.; Steinhilber, D.; Werz, O. Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase Biochem. Pharmacol. 2002, 64, 1767-1775 (Pubitemid 35355728)
52. Koeberle, A.; Siemoneit, U.; Buehring, U.; Northoff, H.; Laufer, S.; Albrecht, W.; Werz, O. Licofelone suppresses prostaglandin E2 formation by interference with the inducible microsomal prostaglandin E2 synthase-1 J. Pharmacol. Exp. Ther. 2008, 326, 975-982
53. Fischer, L.; Szellas, D.; Radmark, O.; Steinhilber, D.; Werz, O. Phosphorylation- and stimulus-dependent inhibition of cellular 5-lipoxygenase activity by nonredox-type inhibitors FASEB J. 2003, 17, 949-951
54. Werz, O.; Burkert, E.; Samuelsson, B.; Radmark, O.; Steinhilber, D. Activation of 5-lipoxygenase by cell stress is calcium independent in human polymorphonuclear leukocytes Blood 2002, 99, 1044-1052 (Pubitemid 34527142)
55. Munoz, E.; Blazquez, M. V.; Ortiz, C.; Gomez-Diaz, C.; Navas, P. Role of ascorbate in the activation of NF-kappaB by tumour necrosis factor-alpha in T-cells Biochem. J. 1997, 325 (Pt 1) 23-28 (Pubitemid 27322681)
56. Schaible, A. M.; Koeberle, A.; Northoff, H.; Lawrenz, B.; Weinigel, C.; Barz, D.; Werz, O.; Pergola, C. High capacity for leukotriene biosynthesis in peripheral blood during pregnancy Prostaglandins, Leukotrienes Essent. Fatty Acids 2013, 89, 245-255