Coupling of a competitive and an irreversible ligand generates mixed type inhibitors of Trypanosoma cruzi trypanothione reductase

Journal of Medicinal Chemistry

Volumn 45, Issue 20, 2002, Pages 4524-4530

  Inhoff, Oliver ^a   Richards, Jonathan M ^b   Brîet, Jan Willem ^b   Lowe, Gordon ^b   Krauth Siegel, R Luise ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

(2 HYDROXYETHANETHIOLATE)(2,2':6',2'' TERPYRIDINE)PLATINUM(II); (TERPYRIDINE)PLATINUM; 2 METHOXY 6 CHLORO 9 AMINOACRIDINE; AMINOACRIDINE DERIVATIVE; ENZYME INHIBITOR; PLATINUM COMPLEX; TRYPANOTHIONE REDUCTASE; TRYPANOTHIONE REDUCTASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CHAGAS DISEASE; DRUG MECHANISM; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME STRUCTURE; NONHUMAN; STRUCTURE ANALYSIS; TRYPANOSOMA CRUZI;

ACRIDINES; AMINOACRIDINES; ANIMALS; ENZYME INHIBITORS; GLUTATHIONE REDUCTASE; HUMANS; LIGANDS; NADH, NADPH OXIDOREDUCTASES; ORGANOPLATINUM COMPOUNDS; TRYPANOCIDAL AGENTS; TRYPANOSOMA CRUZI;

EID: 0037179620     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020885k     Document Type: Article

References (31)

1. Fairlamb, A. H.; Cerami, A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu. Rev. Microbiol. 1992, 46, 695-729.
2. Fairlamb, A. H.; Blackburn, P.; Ulrich, P.; Chait, B. T.; Cerami, A. Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science 1985, 227, 1485-1487.
3. Krieger, S.; Schwarz, W.; Ariyanayagam, M. R.; Fairlamb, A. H.; Krauth-Siegel, R. L.; Clayton, C. Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Mol. Microbiol. 2000, 35, 542-552.
4. Bonse, S.; Santelli-Rouvier, C.; Barbe, J.; Krauth-Siegel, R. L. Inhibition of Trypanosoma cruzi trypanothione reductase by acridines: kinetic studies and structure-activity relationships. J. Med. Chem. 1999, 42, 5448-5454.
5. Jacoby, E. M.; Schlichting, I.; Lantwin, C. B.; Kabsch, W.; Krauth-Siegel, R. L. Crystal structure of the Trypanosoma cruzi trypanothione reductase mepacrine complex. Proteins 1996, 24, 73-80.
6. Krauth-Siegel, R. L.; Coombs, G. H. Enzymes of parasite thiol metabolism as drug targets. Parasitol. Today 1999, 15, 404-409.
7. Austin, S. E.; Khan, M. O.; Douglas, K. T. Rational drug design using trypanothione reductase as a target for anti-trypanosomal and anti-leishmanial drug leads. Drug Des. Discovery 1999, 16, 5-23.
8. Werbovetz, K. A. Target-based drug discovery for malaria, leishmaniasis, and trypanosomiasis. Curr. Med. Chem. 2000, 7, 835-860.
9. Bonse, S.; Richards, J. M.; Ross, S. A.; Lowe, G.; Krauth-Siegel, R. L. (2,2′:6′,2″-Terpyridine)platinum(II) complexes are irreversible inhibitors of Trypanosoma cruzi trypanothione reductase but not of human glutathione reductase. J. Med. Chem. 2000, 43, 4812-4821.
10. Hammond, D. J.; Cover, B.; Gutteridge, W. E. A novel series of chemical structures active in vitro against the trypomastigote form of Trypanosoma cruzi. Trans. R. Soc. Trop. Med. Hyg. 1984, 78, 91-95.
11. Obexer, W.; Schmid, C.; Barbe, J.; Galy, J. P.; Brun, R. Activity and structure relationship of acridine derivatives against African trypanosomes. Trop. Med. Parasitol. 1995, 46, 49-53.
12. Lowe, G.; Droz, A. S.; Vilaivan, T.; Weaver, G. W.; Tweedale, L.; Pratt, J. M.; Rock, P.; Yardley, V.; Croft, S. L. Cytotoxicity of (2,2′:6′,2″-terpyridine)platinum(II) complexes to Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei. J. Med. Chem. 1999, 42, 999-1006.
13. Ross, S. A.; Pitié, M.; Meunier, B. Synthesis of two acridine conjugates of the bis(phenanthroline) ligand "Clip-Phen" and evaluation of the nuclease activity of the corresponding copper complexes. Eur. J. Inorg. Chem. 1999, 557-563.
14. Lowe, G.; Vilaivan, T. An improved method for the synthesis of (2,2′:6′,2″-terpyridine)platinum(II) complexes. J. Chem. Res. 1996, 386-387.
15. Dixon, M.; Webb, E. C. Enzymes; Academic Press: London, 1979.
16. Segel, I. H. Enzyme Kinetics; John Wiley & Sons: New York, 1993.
17. Bisswanger, H. Enzyme Kinetics - Principles and Methods; Wiley-VCH: Weinheim, 2002.
18. Courseille, C.; Busetta, B.; Hospital, M. Structure cristalline et moléculaire de la quinacrine. Acta Crystallogr. 1973, B29, 2349-2355.
19. Garforth, J.; Yin, H.; McKie, J. H.; Douglas, K. T.; Fairlamb, A. H. Rational design of selective ligands for trypanothione reductase from Trypanosoma cruzi. Structural effects on the inhibition by dibenzazepines based on imipramine. J. Enzyme Inhib. 1997, 12, 161-173.
20. Faerman, C. H.; Savvides, S. N.; Strickland, C.; Breidenbach, M. A.; Ponasik, J. A.; Ganem, B.; Ripoll, D.; Krauth-Siegel, R. L.; Karplus, P. A. Charge is the major discriminating factor for glutathione reductase versus trypanothione reductase inhibitors. Bioorg. Med. Chem. 1996, 4, 1247-1253.
21. Savvides, S. N.; Karplus, P. A. Kinetics and crystallographic analysis of human glutathione reductase in complex with a xanthene inhibitor. J. Biol. Chem. 1996, 271, 8101-8107.
22. Karplus, P. A.; Pai, E. F.; Schulz, G. E. A crystallographic study of the glutathione binding site of glutathione reductase at 0.3-nm resolution. Eur. J. Biochem. 1989, 178, 693-703.
23. Schönleben-Janas, A.; Kirsch, P.; Mittl, P. R.; Schirmer, R. H.; Krauth-Siegel, R. L. Inhibition of human glutathione reductase by 10-arylisoalloxazines: crystalline, kinetic, and electrochemical studies. J. Med. Chem. 1996, 39, 1549-1554.
24. Salmon-Chemin, L.; Buisine, E.; Yardley, V.; Kohler, S.; Debreu, M.-A.; Landry, V.; Sergheraert, C.; Croft, S. L.; Krauth-Siegel, R. L.; Davioud-Charvet, E. 2- and 3-Substituted 1,4-naphthoquinone derivatives as subversive substrates of trypanothione reductase and lipoamide dehydrogenase from Trypanosoma cruzi: Synthesis and correlation between redox cycling activities and in vitro cytotoxicity. J. Med. Chem. 2001, 44, 548-565.
25. Kuriyan, J.; Kong, X. P.; Krishna, T. S.; Sweet, R. M.; Murgolo, N. J.; Field, H.; Cerami, A.; Henderson, G. B. X-ray structure of trypanothione reductase from Crithidia fasciculata at 2.4-A resolution. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 8764-8768.
26. Lantwin, C. B.; Schlichting, I.; Kabsch, W.; Pai, E. F.; Krauth-Siegel, R. L. The structure of Trypanosoma cruzi trypanothione reductase in the oxidized and NADPH reduced state. Proteins 1994, 18, 161-173.
27. Chan, C.; Yin, H.; Garforth, J.; McKie, J. H.; Jaouhari, R.; Speers, P.; Douglas, K. T.; Rock, P. J.; Yardley, V.; Croft, S. L.; Fairlamb, A. H. Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs. J. Med. Chem. 1998, 41, 148-156.
28. Lüönd, R. M.; McKie, J. H.; Douglas, K. T.; Dascombe, M. J.; Vale, J. Inhibitors of glutathione reductase as potential antimalarial drugs. Kinetic cooperativity and effect of dimethyl sulphoxide on inhibition kinetics. J. Enzyme Inhib. 1998, 13, 327-345.
29. Sullivan, F. X.; Walsh, C. T. Cloning, sequencing, overproduction and purification of trypanothione reductase from Trypanosoma cruzi. Mol. Biochem. Parasitol. 1991, 44, 145-147.
30. Nordhoff, A.; Bücheler, U. S.; Werner, D.; Schirmer, R. H. Folding of the four domains and dimerization are impaired by the Gly446-Glu exchange in human glutathione reductase. Implications for the design of antiparasitic drugs. Biochemistry 1993, 32, 4060-4066.
31. Jockers-Scherübl, M. C.; Schirmer, R. H.; Krauth-Siegel, R. L. Trypanothione reductase from Trypanosoma cruzi. Catalytic properties of the enzyme and inhibition studies with trypanocidal compounds. Eur. J. Biochem. 1989, 180, 267-272.