Role of human UDP-glucuronosyltransferases in the biotransformation of the triazoloacridinone and imidazoacridinone antitumor agents C-1305 and C-1311: Highly selective substrates for UGT1A10

Drug Metabolism and Disposition

Volumn 40, Issue 9, 2012, Pages 1736-1743

  Fedejko Kap, Barbara ^a   Bratton, Stacie M ^b   Finel, Moshe ^c   Radominska Pandya, Anna ^b   Mazerska, Zofia ^a  

^a GDANSK UNIVERSITY OF TECHNOLOGY   (Poland)

^b UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

^c UNIVERSITY OF HELSINKI   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

5 DIMETHYLAMINOPROPYLAMINO 8 HYDROXYTRIAZOLOACRIDINONE; 8 HYDROXYL GROUP; ACRIDONE DERIVATIVE; ANTINEOPLASTIC AGENT; C 1305; CYTOCHROME P450; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 1A; GLUCURONOSYLTRANSFERASE 1A1; GLUCURONOSYLTRANSFERASE 1A10; GLUCURONOSYLTRANSFERASE 1A3; GLUCURONOSYLTRANSFERASE 1A4; GLUCURONOSYLTRANSFERASE 1A6; GLUCURONOSYLTRANSFERASE 1A7; GLUCURONOSYLTRANSFERASE 2B; GLUCURONOSYLTRANSFERASE 2B15; GLUCURONOSYLTRANSFERASE 2B17; GLUCURONOSYLTRANSFERASE 2B4; GLUCURONOSYLTRANSFERASE 2B7; HYDROXYL GROUP; IMIDACRINE; IMIDAZOACRIDINONE; ISOENZYME; RECOMBINANT ENZYME; TRIAZOLOACRIDINONE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG GLUCURONIDATION; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TRANSFORMATION; ENZYME ACTIVITY; ENZYME SUBSTRATE; GASTROINTESTINAL TRACT; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VIVO STUDY; INTESTINE MUCOSA; ISOLATED ORGAN; LIVER MICROSOME; NONHUMAN; PRIORITY JOURNAL;

ACRIDINES; AMINOACRIDINES; ANTINEOPLASTIC AGENTS; BIOTRANSFORMATION; CATALYSIS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HUMANS; INTESTINES; KINETICS; LIVER; MICROSOMES, LIVER; MODELS, BIOLOGICAL; MUTATION; RECOMBINANT PROTEINS; SUBSTRATE SPECIFICITY; TRIAZOLES;

EID: 84865159571     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.112.045401     Document Type: Article

References (48)

1. Antonio L, Xu J, Little JM, Burchell B, Magdalou J, and Radominska-Pandya A (2003) Glucuronidation of catechols by human hepatic, gastric, and intestinal microsomal UDP-glucuronosyltransferases (UGT) and recombinant UGT1A6, UGT1A9, and UGT2B7. Arch Biochem Biophys 411:251-261. (Pubitemid 36298653)
2. Augustin E, Moś-Rompa A, Skwarska A, Witkowski JM, and Konopa J (2006) Induction of G2/M phase arrest and apoptosis of human leukemia cells by potent antitumor triazoloacridinone C-1305. Biochem Pharmacol 72:1668-1679. (Pubitemid 44765001)
3. Burger AM, Double JA, Konopa J, and Bibby MC (1996) Preclinical evaluation of novel imidazoacridinone derivatives with potent activity against experimental colorectal cancer. Br J Cancer 74:1369-1374. (Pubitemid 26370726)
4. Calabrese CR, Loadman PM, Lim LS, Bibby MC, Double JA, Brown JE, and Lamb JH (1999) In vivo metabolism of the antitumor imidazoacridinone C1311 in the mouse and in vitro comparison with humans. Drug Metab Dispos 27:240-245. (Pubitemid 29072078)
5. Capizzi RL, Roman LA, Tjulandin S, Smirnova I, Manikhas A, Paterson JS, Major A, Lundberg AS, and Fumoleau P (2008) Phase II trial of C1311, a novel inhibitor of topoisomerase II in advanced breast cancer. J Clin Oncol 26 (May 20 Suppl):abstr 1055.
6. Cholody WM, Martelli S, and Konopa J (1990a) 8-Substituted 5-[(aminoalkyl)amino]-6H-v-triazolo[4,5,1-de]acridin-6-ones as potential antineoplastic agents. Synthesis and biological activity. J Med Chem 33:2852-2856. (Pubitemid 20312155)
7. Cholody WM, Martelli S, Paradziej-Lukowicz J, and Konopa J (1990b) 5-[(Aminoalkyl)amino-]imidazo[4,5,1-de]acridin-6-ones as a novel class of antineoplastic agents. Synthesis and biological activity. J Med Chem 33:49-52. (Pubitemid 20038169)
8. Cholody WM, Martelli S, and Konopa J (1992) Chromophore-modified antineoplastic imidazoacridinones. Synthesis and activity against murine leukemias. J Med Chem 35:378-382.
9. Court MH (2005) Isoform-selective probe substrates for in vitro studies of human UDP-glucuronosyltransferases. Meth Enzymol 400:104-116.
10. Cummings J, Ethell BT, Jardine L, Boyd G, Macpherson JS, Burchell B, Smyth JF, and Jodrell DI (2003) Glucuronidation as a mechanism of intrinsic drug resistance in human colon cancer: reversal of resistance by food additives. Cancer Res 63:8443-8450. (Pubitemid 37553155)
11. de Almagro MC, Selga E, Thibaut R, Porte C, Noé V, and Ciudad CJ (2011) UDP-glucuronosyltransferase 1A6 overexpression in breast cancer cells resistant to methotrexate. Biochem Pharmacol 81:60-70.
12. Dziegielewski J and Konopa J (1996) Interstrand crosslinking of DNA induced in tumor cells by a new group of antitumor imidazoacridinones. Proc Am Assoc Cancer Res 37:410.
13. Dziegielewski J, Slusarski B, Konitz A, Skladanowski A, and Konopa J (2002) Intercalation of imidazoacridinones to DNA and its relevance to cytotoxic and antitumor activity. Biochem Pharmacol 63:1653-1662. (Pubitemid 34458004)
14. Fedejko-Kap B, Niemira M, Radominska-Pandya A, and Mazerska Z (2011) Flavin monooxygenases, FMO1 and FMO3, not cytochrome P450 isoenzymes, contribute to metabolism of anti-tumour triazoloacridinone, C-1305, in liver microsomes and HepG2 cells. Xenobiotica 41:1044-1055.
15. Gagnon JF, Bernard O, Villeneuve L, Têtu B, and Guillemette C (2006) Irinotecan inactivation is modulated by epigenetic silencing of UGT1A1 in colon cancer. Clin Cancer Res 12:1850-1858.
16. Harbourt DE, Fallon JK, Ito S, Baba T, Ritter JK, Glish GL, and Smith PC (2012) Quantification of human uridine-diphosphate glucuronosyl transferase 1A isoforms in liver, intestine, and kidney using nanobore liquid chromatography-tandem mass spectrometry. Anal Chem 84:98-105.
17. Höglund C, Sneitz N, Radominska-Pandya A, Laakonen L, and Finel M (2011) Phenylalanine 93 of the human UGT1A10 plays a major role in the interactions of the enzyme with estrogens. Steroids 76:1465-1473.
18. Isambert N, Campone M, Bourbouloux E, Drouin M, Major A, Yin W, Loadman P, Capizzi R, Grieshaber C, and Fumoleau P (2010) Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours. Eur J Cancer 46:729-734.
19. Itäaho K, Court MH, Uutela P, Kostiainen R, Radominska-Pandya A, and Finel M (2009) Dopamine is a low-affinity and high-specificity substrate for the human UDP-glucuronosyltransferase 1A10. Drug Metab Dispos 37:768-775.
20. Klepstad P, Kaasa S, and Borchgrevink PC (2000) Start of oral morphine to cancer patients: effective serum morphine concentrations and contribution from morphine-6-glucuronide to the analgesia produced by morphine. Eur J Clin Pharmacol 55:713-719. (Pubitemid 30077565)
21. Koba M and Konopa J (2007) Interactions of antitumor triazoloacridinones with DNA. Acta Biochim Pol 54:297-306. (Pubitemid 47057873)
22. Konopa J (2001) Antitumor acridines with diaminoalkylo pharmacophoric group. Pure Appl Chem 73:1421-1428.
23. Kostrubsky SE, Sinclair JF, Strom SC, Wood S, Urda E, Stolz DB, Wen YH, Kulkarni S, and Mutlib A (2005) Phenobarbital and phenytoin increased acetaminophen hepatotoxicity due to inhibition of UDP-glucuronosyltransferases in cultured human hepatocytes. Toxicol Sci 87:146-155. (Pubitemid 41222666)
24. Kurkela M, Patana AS, Mackenzie PI, Court MH, Tate CG, Hirvonen J, Goldman A, and Finel M (2007) Interactions with other human UDP- glucuronosyltransferases attenuate the consequences of the Y485D mutation on the activity and substrate affinity of UGT1A6. Pharmacogenet Genomics 17:115-126.
25. Kuśnierczyk H, Chołody WM, Paradziej-Lukowicz J, Radzikowski C, and Konopa J (1994) Experimental antitumor activity and toxicity of the selected triazolo- and imidazoacridinones. Arch Immunol Ther Exp 42:415-423.
26. Lazarus P and Sun D (2010) Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen and aromatase inhibitors. Drug Metab Rev 42:182-194.
27. Lemke K, Poindessous V, Skladanowski A, and Larsen AK (2004) The antitumor triazoloacridone C-1305 is a topoisomerase II poison with unusual properties. Mol Pharmacol 66:1035-1042. (Pubitemid 39319476)
28. Mazerska Z, Dziegielewski J, and Konopa J (2001) Enzymatic activation of a new antitumour drug, 5-diethylaminoethylamino-8-hydroxyimidazoacridinone, C-1311, observed after its intercalation into DNA. Biochem Pharmacol 61:685-694. (Pubitemid 32239421)
29. Mazerska Z, Sowiński P, and Konopa J (2003) Molecular mechanism of the enzymatic oxidation investigated for imidazoacridinone antitumor drug, C-1311. Biochem Pharmacol 66:1727-1736. (Pubitemid 37249317)
30. Miller GP, Lichti CF, Zielinska AK, Mazur A, Bratton SM, Gallus-Zawada A, Finel M, Moran JH, and Radominska-Pandya A (2008) Identification of hydroxywarfarin binding site in human UDP glucuronosyltransferase 1a10: phenylalanine90 is crucial for the glucuronidation of 6-and 7-hydroxywarfarin but not 8-hydroxywarfarin. Drug Metab Dispos 36:2211-2218.
31. Murthy BR, Pollack GM, and Brouwer KL (2002) Contribution of morphine-6-glucuronide to antinociception following intravenous administration of morphine to healthy volunteers. J Clin Pharmacol 42:569-576. (Pubitemid 34438556)
32. Osborne R, Thompson P, Joel S, Trew D, Patel N, and Slevin M (1992) The analgesic activity of morphine-6-glucuronide. Br J Clin Pharmacol 34:130-138.
33. Potega A, Dabrowska E, Niemira M, Kot-Wasik A, Ronseaux S, Henderson CJ, Wolf CR, and Mazerska Z (2011) The imidazoacridinone antitumor drug, C-1311, is metabolized by flavin monooxygenases but not by cytochrome P450s. Drug Metab Dispos 39:1423-1432.
34. Ritter JK (2000) Roles of glucuronidation and UDP- glucuronosyltransferases in xenobiotic bioactivation reactions. Chem Biol Interact 129:171-193.
35. Sallustio BC, Degraaf YC, Weekley JS, and Burcham PC (2006) Bioactivation of carboxylic acid compounds by UDP-Glucuronosyltransferases to DNA-damaging intermediates: role of glycoxidation and oxidative stress in genotoxicity. Chem Res Toxicol 19:683-691. (Pubitemid 43800985)
36. Sabolovic N, Humbert AC, Radominska-Pandya A, and Magdalou J (2006) Resveratrol is efficiently glucuronidated by UDP-glucuronosyltransferases in the human gastrointestinal tract and in Caco-2 cells. Biopharm Drug Dispos 27:181-189. (Pubitemid 43797114)
37. Skladanowski A, Plisov SY, Konopa J, and Larsen AK (1996) Inhibition of DNA topoisomerase II by imidazoacridinones, new antineoplastic agents with strong activity against solid tumors. Mol Pharmacol 49:772-780. (Pubitemid 26149906)
38. Skwarska A, Augustin E, and Konopa J (2007) Sequential induction of mitotic catastrophe followed by apoptosis in human leukemia MOLT4 cells by imidazoacridinone C-1311. Apoptosis 12:2245-2257. (Pubitemid 350077255)
39. Smith SC, Havaleshko DM, Moon K, Baras AS, Lee J, Bekiranov S, Burke DJ, and Theodorescu D (2011) Use of yeast chemigenomics and COXEN informatics in preclinical evaluation of anticancer agents. Neoplasia 13:72-80.
40. Starlard-Davenport A, Xiong Y, Bratton S, Gallus-Zawada A, Finel M, and Radominska-Pandya A (2007) Phenylalanine(90) and phenylalanine(93) are crucial amino acids within the estrogen binding site of the human UDP- glucuronosyltransferase 1A10. Steroids 72:85-94. (Pubitemid 46037767)
41. Starlard-Davenport A, Lyn-Cook B, Beland FA, and Pogribny IP (2010) The role of UDP-glucuronosyltransferases and drug transporters in breast cancer drug resistance. Exp Oncol. 32:172-180.
42. Tallman MN, Miles KK, Kessler FK, Nielsen JN, Tian X, Ritter JK, and Smith PC (2007) The contribution of intestinal UDP-glucuronosyltransferases in modulating 7-ethyl-10-hydroxy-camptothecin (SN-38)-induced gastrointestinal toxicity in rats. J Pharmacol Exp Ther 320:29-37. (Pubitemid 46025716)
43. Thomas AL, Anthoney A, Scott E, Ahmed S, Lundberg AS, Major A, Capizzi RL, and Twelves CJ (2008) C-1311, a novel inhibitor of FLT3 and topoisomerase II: a phase 1 trial of a once every three week schedule in patients with advanced solid tumors (Abstract). J Clin Oncol 26 (Suppl):2576.
44. Xiong Y, Bernardi D, Bratton S, Ward MD, Battaglia E, Finel M, Drake RR, and Radominska-Pandya A (2006) Phenylalanine 90 and 93 are localized within the phenol binding site of human UDP-glucuronosyltransferase 1A10 as determined by photoaffinity labeling, mass spectrometry, and site-directed mutagenesis. Biochemistry 45:2322-2332. (Pubitemid 43271332)
45. Xiong Y, Patana AS, Miley MJ, Zielinska AK, Bratton SM, Miller GP, Goldman A, Finel M, Redinbo MR, and Radominska-Pandya A (2008) The first aspartic acid of the DQxD motif for human UDP-glucuronosyltransferase 1A10 interacts with UDP-glucuronic acid during catalysis. Drug Metab Dispos 36:517-522. (Pubitemid 351397976)
46. Zheng Z, Park JY, Guillemette C, Schantz SP, and Lazarus P (2001) Tobacco carcinogen-detoxifying enzyme UGT1A7 and its association with orolaryngeal cancer risk. J Natl Cancer Inst 93:1411-1418. (Pubitemid 32936819)
47. Zheng Z, Fang JL, and Lazarus P (2002) Glucuronidation: an important mechanism for detoxification of benzo[a]pyrene metabolites in aerodigestive tract tissues. Drug Metab Dispos 30:397-403. (Pubitemid 34263824)
48. Zielinska A, Lichti CF, Bratton S, Mitchell NC, Gallus-Zawada A, Le VH, Finel M, Miller GP, Radominska-Pandya A, and Moran JH (2008) Glucuronidation of monohydroxylated warfarin metabolites by human liver microsomes and human recombinant UDP-glucuronosyltransferases. J Pharmacol Exp Ther 324:139-148. (Pubitemid 350294175)