Bioactivation potential of thiophene-containing drugs

Chemical Research in Toxicology

Volumn 27, Issue 8, 2014, Pages 1344-1358

  Gramec, Darja ^a   Peterlin Mašič, Lucija ^a   Sollner Dolenc, Marija ^a  

^a UNIVERSITY OF LJUBLJANA   (Slovenia)

Author keywords

[No Author keywords available]

Indexed keywords

CLOPIDOGREL; DULOXETINE; EPROSARTAN; METHAPYRILENE; OLANZAPINE; OSI 930; PRASUGREL; RIVAROXABAN; SUPROFEN; THIOPHENE DERIVATIVE; TIAPROFENIC ACID; TICLOPIDINE; TIENILIC ACID; UNCLASSIFIED DRUG; ZILEUTON; ANTIDEPRESSANT AGENT; ANTITHROMBOCYTIC AGENT; CYTOCHROME P450;

COVALENT BOND; DRUG DETOXIFICATION; DRUG METABOLISM; DRUG STRUCTURE; EPOXIDATION; HUMAN; ISOMER; OXIDATION; REVIEW; STRUCTURE ACTIVITY RELATION; CHEMISTRY; DEPRESSION; HEPATITIS; METABOLISM;

ANTIDEPRESSIVE AGENTS; CYTOCHROME P-450 ENZYME SYSTEM; DEPRESSION; HEPATITIS; HUMANS; PLATELET AGGREGATION INHIBITORS; THIOPHENES; TICRYNAFEN;

EID: 84906254736     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx500134g     Document Type: Review

References (70)

1. Attia, S. M. (2010) Deleterious effects of reactive metabolites Oxid. Med. Cell. Longevity 3, 238-253
2. Park, B. K., Laverty, H., Srivastava, A., Antoine, D. J., Naisbitt, D., and Williams, D. P. (2011) Drug bioactivation and protein adduct formation in the pathogenesis of drug-induced toxicity Chem.-Biol. Interact. 192, 30-36
3. Kalgutkar, A. S. (2009) Role of bioactivation in idiosyncratic drug toxicity: structure-toxicity relationships, in Advances in Bioactivation Research (Elfarra, A., Ed.) Springer, New York.
4. Uetrecht, J. (2008) Idiosyncratic drug reactions: past, present, and future Chem. Res. Toxicol. 21, 84-92
5. Li, A. P. (2002) A review of the common properties of drugs with idiosyncratic hepatotoxicity and the "multiple determinant hypothesis" for the manifestation of idiosyncratic drug toxicity Chem.-Biol. Interact. 142, 7-23
6. Stepan, A. F., Walker, D. P., Bauman, J., Price, D. A., Baillie, T. A., Kalgutkar, A. S., and Aleo, M. D. (2011) Structural alert/reactive metabolite concept as applied in medicinal chemistry to mitigate the risk of idiosyncratic drug toxicity: a perspective based on the critical examination of trends in the top 200 drugs marketed in the United States Chem. Res. Toxicol. 24, 1345-1410
7. Dalvie, D. K., Kalgutkar, A. S., Khojasteh-Bakht, S. C., Obach, R. S., and ODonnell, J. P. (2002) Biotransformation reactions of five-membered aromatic heterocyclic rings Chem. Res. Toxicol. 15, 269-299
8. Valadon, P., Dansette, P. M., Girault, J. P., Amar, C., and Mansuy, D. (1996) Thiophene sulfoxides as reactive metabolites: formation upon microsomal oxidation of a 3-aroylthiophene and fate in the presence of nucleophiles in vitro and in vivo Chem. Res. Toxicol. 9, 1403-1413
9. Dansette, P. M., Bertho, G., and Mansuy, D. (2005) First evidence that cytochrome P450 may catalyze both S-oxidation and epoxidation of thiophene derivatives Biochem. Biophys. Res. Commun. 338, 450-455
10. Mansuy, D. and Dansette, P. M. (2011) Sulfenic acids as reactive intermediates in xenobiotic metabolism Arch. Biochem. Biophys. 507, 174-185
11. Lecoeur, S., Bonierbale, E., Challine, D., Gautier, J. C., Valadon, P., Dansette, P. M., Catinot, R., Ballet, F., Mansuy, D., and Beaune, P. H. (1994) Specificity of in vitro covalent binding of tienilic acid metabolites to human liver microsomes in relationship to the type of hepatotoxicity: comparison with two directly hepatotoxic drugs Chem. Res. Toxicol. 7, 434-442
12. Bonierbale, E., Valadon, P., Pons, C., Desfosses, B., Dansette, P. M., and Mansuy, D. (1999) Opposite behaviors of reactive metabolites of tienilic acid and its isomer toward liver proteins: use of specific anti-tienilic acid-protein adduct antibodies and the possible relationship with different hepatotoxic effects of the two compounds Chem. Res. Toxicol. 12, 286-296
13. Nishiya, T., Kataoka, H., Mori, K., Goto, M., Sugawara, T., and Furuhama, K. (2006) Tienilic acid enhances hyperbilirubinemia in Eisai hyperbilirubinuria rats through hepatic multidrug resistance-associated protein 3 and heme oxygenase-1 induction Toxicol. Sci. 91, 651-659
14. ODonnell, J. P., Dalvie, D. K., Kalgutkar, A. S., and Obach, R. S. (2003) Mechanism-based inactivation of human recombinant P450 2C9 by the nonsteroidal anti-inflammatory drug suprofen Drug Metab. Dispos. 31, 1369-1377
15. Chan, C. Y., New, L. S., Ho, H. K., and Chan, E. C. (2011) Reversible time-dependent inhibition of cytochrome P450 enzymes by duloxetine and inertness of its thiophene ring towards bioactivation Toxicol. Lett. 206, 314-324
16. Pereillo, J. M., Maftouh, M., Andrieu, A., Uzabiaga, M. F., Fedeli, O., Savi, P., Pascal, M., Herbert, J. M., Maffrand, J. P., and Picard, C. (2002) Structure and stereochemistry of the active metabolite of clopidogrel Drug Metab. Dispos. 30, 1288-1295
17. Farid, N. A., Kurihara, A., and Wrighton, S. A. (2010) Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans J. Clin. Pharmacol. 50, 126-142
18. Medower, C., Wen, L., and Johnson, W. W. (2008) Cytochrome P450 oxidation of the thiophene-containing anticancer drug 3-[(quinolin-4-ylmethyl)-amino]- thiophene-2-carboxylic acid (4-trifluoromethoxy-phenyl)-amide to an electrophilic intermediate Chem. Res. Toxicol. 21, 1570-1577
19. Dreiem, A. and Fonnum, F. (2004) Thiophene is toxic to cerebellar granule cells in culture after bioactivation by rat liver enzymes Neurotoxicology 25, 959-966
20. Bray, H. G., Carpanini, F. M., and Waters, B. D. (1971) The metabolism of thiophen in the rabbit and the rat Xenobiotica 1, 157-168
21. Mansuy, D., Valadon, P., Erdelmeier, I., Lopez-Garcia, P., Amar, C., Girault, J. P., and Dansette, P. M. (1991) Thiophene S-Oxides as new RM: formation by Cytochrome P450 dependent oxidation and reaction with nucleophiles J. Am. Chem. Soc. 113, 7825-7826
22. Treiber, A., Dansette, P., Amri, H., Girault, J., Ginderow, D., Mornon, J. P., and Mansuy, D. (1997) Chemical and biological oxidation of thiophene: preparation and complete characterization of thiophene S-oxide dimers and evidence for thiophene S-oxide as an intermediate in thiophene metabolism in vivo and in vitro J. Am. Chem. Soc. 119, 1565-1571
23. Dansette, P. M., Rosi, J., Bertho, G., and Mansuy, D. (2012) Cytochromes P450 catalyze both steps of the major pathway of clopidogrel bioactivation, whereas paraoxonase catalyzes the formation of a minor thiol metabolite isomer Chem. Res. Toxicol. 25, 348-356
24. (2008) The Practice of Medicinal Chemistry (Wermuth, C. G., Ed.) 3 rd ed, Elsevier, Amsterdam, The Netherlands.
25. Dansette, P. M., Libraire, J., Bertho, G., and Mansuy, D. (2009) Metabolic oxidative cleavage of thioesters: evidence for the formation of sulfenic acid intermediates in the bioactivation of the antithrombotic prodrugs ticlopidine and clopidogrel Chem. Res. Toxicol. 22, 369-373
26. Rademacher, P. M., Woods, C. M., Huang, Q., Szklarz, G. D., and Nelson, S. D. (2012) Differential oxidation of two thiophene-containing regioisomers to reactive metabolites by cytochrome P450 2C9 Chem. Res. Toxicol. 25, 895-903
27. Lemieux, G., Beauchemin, M., Gougoux, A., and Vinay, P. (1978) Treatment of arterial hypertension with tienilic acid, a new diuretic with uricosuric properties Can. Med. Assoc. J. 118, 1074-1078
28. Lau, K., Stote, R. M., Goldberg, M., and Agus, Z. S. (1977) Mechanisms of the uricosuric effect of the diuretic tienilic acid (Ticrynafen) in man Clin. Sci. Mol. Med. 53, 379-386
29. López-García, M. P., Dansette, P. M., and Coloma, J. (2005) Kinetics of tienilic acid bioactivation and functional generation of drug-protein adducts in intact rat hepatocytes Biochem. Pharmacol. 70, 1870-1882
30. Graham, E. E., Walsh, R. J., Hirst, C. M., Maggs, J. L., Martin, S., Wild, M. J., Wilson, I. D., Harding, J. R., Kenna, J. G., Peter, R. M., Williams, D. P., and Park, B. K. (2008) Identification of the thiophene ring of methapyrilene as a novel bioactivation-dependent hepatic toxicophore J. Pharmacol. Exp. Ther. 326, 657-671
31. Ratra, G. S., Morgan, W. A., Mullervy, J., Powell, C. J., and Wright, M. C. (1998) Methapyrilene hepatotoxicity is associated with oxidative stress, mitochondrial disfunction and is prevented by the Ca2+ channel blocker verapamil Toxicology 130, 79-93
32. Ratra, G. S., Powell, C. J., Park, B. K., Maggs, J. L., and Cottrell, S. (2000) Methapyrilene hepatotoxicity is associated with increased hepatic glutathione, the formation of glucuronide conjugates, and enterohepatic recirculation Chem.-Biol. Interact. 129, 279-295
33. Ratra, G. S., Cottrell, S., and Powell, C. J. (1998) Effects of induction and inhibition of cytochromes P450 on the hepatotoxicity of methapyrilene Toxicol. Sci. 46, 185-196
34. Crawford, M. L., Waller, P. C., and Wood, S. M. (1997) Severe cystitis associated with tiaprofenic acid Br. J. Urol. 79, 578-584
35. Hart, D., Ward, M., and Lifschitz, M. D. (1987) Suprofen-related nephrotoxicity. A distinct clinical syndrome Ann. Intern. Med. 106, 235-238
36. Joshi, E. M., Heasley, B. H., Chordia, M. D., and Macdonald, T. L. (2004) In vitro metabolism of 2-acetylbenzothiophene: relevance to zileuton hepatotoxicity Chem. Res. Toxicol. 17, 137-143
37. Coen, M., Rademacher, P. M., Zou, W., Scott, M., Ganey, P. E., Roth, R., and Nelson, S. D. (2012) Comparative NMR-based metabonomic investigation of the metabolic phenotype associated with tienilic acid and tienilic acid isomer Chem. Res. Toxicol. 25, 2412-2422
38. New Zealand Hypertension Study Group (1983) Multicentre controlled trial of tienilic acid in hyperuricaemic, hypertensive subjects, with intensive monitoring of liver function Br. J. Clin. Pharmacol. 15, 513-518
39. López-Garcia, M. P., Dansette, P. M., and Mansuy, D. (1994) Thiophene derivatives as new mechanism-based inhibitors of cytochromes P-450: inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid Biochemistry 33, 166-175
40. Koenigs, L. L., Peter, R. M., Hunter, A. P., Haining, R. L., Rettie, A. E., Friedberg, T., Pritchard, M. P., Shou, M., Rushmore, T. H., and Trager, W. F. (1999) Electrospray ionization mass spectrometric analysis of intact cytochrome P450: identification of tienilic acid adducts to P450 2C9 Biochemistry 38, 2312-2319
41. Mancy, A., Broto, P., Dijols, S., Dansette, P. M., and Mansuy, D. (1995) The substrate binding site of human liver cytochrome P450 2C9: an approach using designed tienilic acid derivatives and molecular modeling Biochemistry 34, 10365-10375
42. Melet, A., Assrir, N., Jean, P., Pilar Lopez-Garcia, M., Marques-Soares, C., Jaouen, M., Dansette, P. M., Sari, M. A., and Mansuy, D. (2003) Substrate selectivity of human cytochrome P450 2C9: importance of residues 476, 365, and 114 in recognition of diclofenac and sulfaphenazole and in mechanism-based inactivation by tienilic acid Arch. Biochem. Biophys. 409, 80-91
43. Smith, D. A., van de Waterbeemd, H., and Walker, D. K. (2001) Pharmacokinetics and Metabolism in Drug Design, Wiley, New York.
44. Beaune, P., Dansette, P. M., Mansuy, D., Kiffel, L., Finck, M., Amar, C., Leroux, J. P., and Homberg, J. C. (1987) Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug Proc. Natl. Acad. Sci. U.S.A. 84, 551-555
45. Chen, W., Caceres-Cortes, J., Zhang, H., Zhang, D., Humphreys, W. G., and Gan, J. (2011) Bioactivation of substituted thiophenes including α-chlorothiophene-containing compounds in human liver microsomes Chem. Res. Toxicol. 24, 663-669
46. Mansuy, D. (1997) Molecular structure and hepatotoxicity: compared data about two closely related thiophene compounds J. Hepatol. 26, 22-25
47. Hutzler, J. M., Balogh, L. M., Zientek, M., Kumar, V., and Tracy, T. S. (2009) Mechanism-based inactivation of cytochrome P450 2C9 by tienilic acid and (±)-suprofen: a comparison of kinetics and probe substrate selection Drug Metab. Dispos. 37, 59-65
48. Wang, M. H., Brand-Schieber, E., Zand, B. A., Nguyen, X., Falck, J. R., Balu, N., and Schwartzman, M. L. (1998) Cytochrome P450-derived arachidonic acid metabolism in the rat kidney: characterization of selective inhibitors J. Pharmacol. Exp. Ther. 284, 966-973
49. Wu, W. Y., Wang, G., Ball, S. G., Desaiah, D., and Ang, Q. Q. (2011) Duloxetine versus placebo in the treatment of patients with generalized anxiety disorder in China Chin. Med. J. 124, 3260-3268
50. Dhillon, S. (2013) Duloxetine: a review of its use in the management of major depressive disorder in older adults Drugs Aging 30, 59-79
51. Pergolizzi, J. V., Raffa, R. B., Taylor, R., Rodriguez, G., Nalamachu, S., and Langley, P. (2013) A review of duloxetine 60 mg once-daily dosing for the management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic osteoarthritis pain and low back pain Pain Pract. 13, 239-252
52. Lantz, R. J., Gillespie, T. A., Rash, T. J., Kuo, F., Skinner, M., Kuan, H. Y., and Knadler, M. P. (2003) Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects Drug Metab. Dispos. 31, 1142-1150
53. Carter, N. J. and McCormack, P. L. (2009) Duloxetine: a review of its use in the treatment of generalized anxiety disorder CNS Drugs 23, 523-541
54. Schmidt, B. and Schieffer, B. (2003) Angiotensin II AT1 receptor antagonists. Clinical implications of active metabolites J. Med. Chem. 46, 2261-2270
55. McClellan, K. J. and Balfour, J. A. (1998) Eprosartan Drugs 55, 713-718
56. Wu, G., Vashishtha, S. C., and Erve, J. C. (2010) Characterization of glutathione conjugates of duloxetine by mass spectrometry and evaluation of in silico approaches to rationalize the site of conjugation for thiophene containing drugs Chem. Res. Toxicol. 23, 1393-1404
57. Weinz, C., Schwarz, T., Kubitza, D., Mueck, W., and Lang, D. (2009) Metabolism and excretion of rivaroxaban, an oral, direct factor Xa inhibitor, in rats, dogs, and humans Drug Metab. Dispos. 37, 1056-1064
58. Callaghan, J. T., Bergstrom, R. F., Ptak, L. R., and Beasley, C. M. (1999) Olanzapine. Pharmacokinetic and pharmacodynamic profile Clin. Pharmacokinet. 37, 177-193
59. Kazui, M., Nishiya, Y., Ishizuka, T., Hagihara, K., Farid, N. A., Okazaki, O., Ikeda, T., and Kurihara, A. (2010) Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite Drug Metab. Dispos. 38, 92-99
60. Dansette, P. M., Levent, D., Hessani, A., Bertho, G., and Mansuy, D. (2013) Thiolactone sulfoxides as new reactive metabolites acting as bis-electrophiles: implication in clopidogrel and prasugrel bioactivation Chem. Res. Toxicol. 26, 794-802
61. Wallentin, L. (2009) P2Y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use Eur. Heart J. 30, 1964-1977
62. Shimizu, S., Atsumi, R., Nakazawa, T., Fujimaki, Y., Sudo, K., and Okazaki, O. (2009) Metabolism of ticlopidine in rats: identification of the main biliary metabolite as a glutathione conjugate of ticlopidine S-oxide Drug Metab. Dispos. 37, 1904-1915
63. Richter, T., Mürdter, T. E., Heinkele, G., Pleiss, J., Tatzel, S., Schwab, M., Eichelbaum, M., and Zanger, U. M. (2004) Potent mechanism-based inhibition of human CYP2B6 by clopidogrel and ticlopidine J. Pharmacol. Exp. Ther. 308, 189-197
64. Lammert, C., Einarsson, S., Saha, C., Niklasson, A., Bjornsson, E., and Chalasani, N. (2008) Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: search for signals Hepatology 47, 2003-2009
65. Nakayama, S., Atsumi, R., Takakusa, H., Kobayashi, Y., Kurihara, A., Nagai, Y., Nakai, D., and Okazaki, O. (2009) A zone classification system for risk assessment of idiosyncratic drug toxicity using daily dose and covalent binding Drug Metab. Dispos. 37, 1970-1977
66. Hu, Y., Yang, S., Shilliday, F. B., Heyde, B. R., Mandrell, K. M., Robins, R. H., Xie, J., Reding, M. T., Lai, Y., and Thompson, D. C. (2010) Novel metabolic bioactivation mechanism for a series of anti-inflammatory agents (2,5-diaminothiophene derivatives) mediated by cytochrome p450 enzymes Drug Metab. Dispos. 38, 1522-1531
67. (2010) Thelin (sitaxentan) to be withdrawn due to cases of unpredictable serious liver injury, European Medicines Agency Press Release, London.
68. Erve, J. C., Gauby, S., Maynard, J. W., Svensson, M. A., Tonn, G., and Quinn, K. P. (2013) Bioactivation of sitaxentan in liver microsomes, hepatocytes, and expressed human P450s with characterization of the glutathione conjugate by liquid chromatography tandem mass spectrometry Chem. Res. Toxicol. 26, 926-936
69. Dalvie, D., Kang, P., Zientek, M., Xiang, C., Zhou, S., and Obach, R. S. (2008) Effect of intestinal glucuronidation in limiting hepatic exposure and bioactivation of raloxifene in humans and rats Chem. Res. Toxicol. 21, 2260-2271
70. Kemp, D. C., Fan, P. W., and Stevens, J. C. (2002) Characterization of raloxifene glucuronidation in vitro: contribution of intestinal metabolism to presystemic clearance Drug Metab. Dispos. 30, 694-700