Inhibition of Trypanosoma cruzi trypanothione reductase by acridines: Kinetic studies and structure-activity relationships

Journal of Medicinal Chemistry

Volumn 42, Issue 26, 1999, Pages 5448-5454

  Bonse, Susanne ^a   Santelli Rouvier, Christiane ^b   Barbe, Jacques ^b   Krauth Siegel, R Luise ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

9 THIOACRIDINE DERIVATIVE; ACRIDINE DERIVATIVE; AMINOACRIDINE; TRYPANOTHIONE REDUCTASE; UNCLASSIFIED DRUG;

ARTICLE; CHAGAS DISEASE; DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; NONHUMAN; STRUCTURE ACTIVITY RELATION; TRYPANOSOMA CRUZI;

ACRIDINES; ANIMALS; ENZYME INHIBITORS; KINETICS; MAGNETIC RESONANCE SPECTROSCOPY; NADH, NADPH OXIDOREDUCTASES; STRUCTURE-ACTIVITY RELATIONSHIP; TRYPANOSOMA CRUZI;

EID: 0033619994     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990386s     Document Type: Article

References (47)

1. Fairlamb, A. H.; Cerami, A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu. Rev. Microbiol. 1992, 46, 695-729.
2. Montrichard, F.; Le Guen, F.; Laval-Martin, D. L.; Davioud-Charvet, E. Evidence for the coexistence of glutathione reductase and trypanothione reductase in the nontrypanosomatid Euglenozoa: Euglena gracilis Z. FEBS Lett. 1999, 442, 29-33.
3. 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.
4. 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 Å resolution. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 8764-8768.
5. Hunter, W. N.; Bailey, S.; Habash, J.; Harrop, S. J.; Helliwell, J. R.; Aboagye-Kwarteng, T.; Smith, K.; Fairlamb, A. H. Active site of trypanothione reductase. A target for rational drug design. J. Mol. Biol. 1992, 227, 322-333.
6. 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.
7. Stoll, V. S.; Simpson, S. J.; Krauth-Siegel, R. L.; Walsh, C. T.; Pai, E. F. Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity. Biochemistry 1997, 36, 6437-6447.
8. 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.
9. Dumas, C.; Ouellette, M.; Tovar, J.; Cunningham, M. L.; Fairlamb, A. H.; Tamar, S.; Olivier, M.; Papadopoulou, B. Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. EMBO J. 1997, 16, 2590-2598.
10. Tovar, J.; Cunningham, M. L.; Smith, A. C.; Croft, S. L.; Fairlamb, A. H. Down-regulation of Leishmania donovani trypanothione reductase by heterologous expression of a transdominant mutant homologue: effect on parasite intracellular survival. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 5311-5316.
11. Krieger, S.; Schwarz, W.; Ariyanayagam, M. R.; Fairlamb, A. H.; Krauth-Siegel, R. L.; Clayton, C. H. Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Mol. Microbiol., in press.
12. 1-glutathionylspermidine disulphide at 0.28-nm resolution. Eur. J. Biochem. 1993, 213, 67-75.
13. Bond, C. S.; Zhang, Y.; Berriman, M.; Cunningham, M. L.; Fairlamb, A. H.; Hunter, W. N. Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure 1999, 7, 81-89.
14. Jacoby, E. M.; Schlichting, I.; Lantwin, C. B.; Kabach, W.; Krauth-Siegel, R. L. Crystal structure of the Trypanosoma cruzi trypanothione reductase mepacrine complex. Proteins 1996, 24, 73-80.
15. Schirmer, R. H.; Müller, J. G.; Krauth-Siegel, R. L. Disulfide-reductase inhibitors as chemotherapeutic agents: The design of drugs for trypanosomiasis and malaria. Angew. Chem., Int. Ed. Engl. 1995, 34, 141-154.
16. Krauth-Siegel, R. L.; Schöneck, R. Flavoprotein structure and mechanism. 5. Trypanothione reductase and lipoamide dehydrogenase as targets for a structure-based drug design. FASEB J. 1995, 9, 1138-1146.
17. Krauth-Siegel, R. L.; Coombs, G. H. Enzymes of parasite thiol metabolism as drug targets. Parasitol. Today 1999, 15, 404-409.
18. Krauth-Siegel, R. L.; Lohrer, H.; Bücheler, U. S.; Schirmer, R. H. The antioxidant enzymes glutathione reductase and trypanothione reductase as drug targets. In Biochemical Protozoology; Coombs, G., North, M., Eds; Taylor & Francis: London, 1991; pp 493-506.
19. Benson, T. J.; McKie, J. H.; Garforth, J.; Borges, A.; Fairlamb, A. H.; Douglas, K. T. Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures. Biochem. J. 1992, 286, 9-11.
20. Krauth-Siegel, R. L.; Jacoby, E. M.; Jockers-Scherübl, M. C.; Schlichting, I.; Barbe, J. T. cruzi trypanothione reductase: structure-function relationships of enzyme-inhibitor complexes. In Flavins and Flavoproteins; Stevenson, K. J., Massey, V., Williams, C. H., Jr., Eds.; University of Calgary Press: Canada, 1996; pp 35-44.
21. 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.
22. Girault, S.; Davioud-Charvet, E.; Salmon, L.; Berecibar, A.; Debreu, M. A.; Sergheraert, C. Structure-activity relationships in 2-aminodiphenylsulfides against trypanothione reductase from Trypanosoma cruzi. Bioorg. Med. Chem. Lett. 1998, 8, 1175-1180.
23. Hammond, D. J.; Cover, B.; Gutteridge, E. W. 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.
24. 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.
25. Albert, A. The Acridines; Edward Arnold: London, 1966.
26. Shepard, E. R.; Shonle, H. A. Nuclear substituted 9-(4′-diethylamino-1′-methylbutylamino)-acridines. J. Am. Chem. Soc. 1948, 70, 1979-1980.
27. Borch, R. F.; Bernstein, M. D.; Durst, H. D. The cyanohydridoborate anion as a selective reducing agent. J. Am. Chem. Soc. 1971, 93, 2897-2904.
28. Breslow, D. S.; Yost, R. S.; Walker, H. G.; Hauser, C. R. Synthesis of atabrine analogues having various aliphatic a-substituents in the side chain. J. Am. Chem. Soc. 1944, 66, 1-1924.
29. Bsiri, N.; Johnson, C.; Kayirere, M.; Galy, A. M.; Galy, J. P.; Barbe, J.; Osuna, A.; Mesa-Valle, M. C.; Castilla Calvente, J. J.; Rodriguez-Cabezas, M. N. Trypanocidal structure-activity relationship in 9-thioalkylacridines. Ann. Pharm. Fr. 1996, 54, 27-33.
30. Segel, I. H. Enzyme kinetics; John Wiley & Sons: New York, 1993.
31. Dixon, M.; Webb, E. C. Enzymes; Academic Press: London, 1979.
32. 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.
33. Wlodek, S. T.; Antosiewicz, J.; McCammon, J. A.; Straatsma, T. P.; Gilson, M. K.; Briggs, J. M.; Humblet, C.; Sussman, J. L. Binding of tacrine and 6-chlorotacrine by acetylcholinesterase. Biopolymers 1996, 38, 109-117.
34. Cornish-Bowden, A. A simple graphical method for determining the inhibition constants of mixed, uncompetitive and noncompetitive inhibitors. Biochem. J. 1974, 137, 143-144.
35. 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.
36. 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.
37. 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.
38. Bilzer, M.; Krauth-Siegel, R. L.; Schirmer, R. H.; Akerboom, T. P.; Sies, H.; Schulz, G. E. Interaction of a glutathione S-conjugate with glutathione reductase. Kinetic and X-ray crystallographic studies. Eur. J. Biochem. 1984, 138, 373-378.
39. Horvath, D. A virtual screening approach applied to the search for trypanothione reductase inhibitors. J. Med. Chem. 1997, 40, 2412-2423.
40. Becker, K.; Christopherson, R. I.; Cowden, W. B.; Hunt, N. H.; Schirmer, R. H. Flavin analogues with antimalarial activity as glutathione reductase inhibitors. Biochem. Pharmacol. 1990, 39, 59-65.
41. Sullivan, F. X.; Walsh, C. T. Cloning, sequencing, overproduction and purification of trypanothione reductase from Trypanosoma cruzi. Mol. Biochem. Parasitol. 1991, 44, 145-147.
42. 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.
43. Albert, A.; Dyer, F. J.; Linnel, W. H. Chemotherapeutic studies in the acridine series. IV Relation between structure and toxicity. Q. J. Pharm. Pharmacol. 1937, 10, 649-658.
44. Holliman, F. G.; Mann, F. G. Synthetic application of o-β-bromoethylbenzyl bromide. J. Chem. Soc. 1945, 34-37.
45. Cherntsov, O. M.; Drozdov, N. S. The preparation and antimalarial action of substituted 9-aminoacridine. Zh. Obshchei. Khim. 1939, 9, 1435-1440.
46. Mietzsch, F.; Mauss, H. I. I. G. Farben, Deutsches Patent, 553,072. Chem. Abstr. 1932, 4683.
47. Galy, J. P.; Vincent, E. J.; Galy, A. M.; Barbe, J.; Elguero, J. A comparative study of reactivity of acridanones, aminoacridines and thioacridanones toward alkylating agents using phase transfer catalysis. Bull. Soc. Chim. Belg. 1981, 90, 947-954.