Parasite-specific trypanothione reductase as a drug target molecule

Parasitology Research

Volumn 90, Issue SUPPL. 2, 2003, Pages

  Krauth Siegel, R Luise ^a   Inhoff, Oliver ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 NAPHTHOQUINONE; ACRIDINE; AJOENE; ANTIDEPRESSANT AGENT; ANTIHYPERTENSIVE AGENT; BENZOQUINONE; CARMUSTINE; CEPHARANTHINE; CHLORPROMAZINE; CLOMIPRAMINE; CRYSTAL VIOLET; DIBENZAZEPINE DERIVATIVE; GLUTATHIONE; GLUTATHIONE REDUCTASE; IMIPRAMINE; ISOQUINOLINE DERIVATIVE; MEPACRINE; NITROFURAN DERIVATIVE; NITROSOUREA DERIVATIVE; PEPTIDE DERIVATIVE; PHENOTHIAZINE DERIVATIVE; PLUMBAGIN; POLYAMINE; PYRONARIDINE; QUINOLINE DERIVATIVE; SPERMIDINE DERIVATIVE; SPERMINE DERIVATIVE; TETRACYCLIC ANTIDEPRESSANT AGENT; TRYPANOTHIONE REDUCTASE; UNINDEXED DRUG;

AFRICAN TRYPANOSOMIASIS; CHAGAS DISEASE; DRUG ACTIVITY; DRUG POTENCY; DRUG SENSITIVITY; DRUG STRUCTURE; ENZYME INHIBITION; HOST; HUMAN; IN VITRO STUDY; LEISHMANIA DONOVANI; LEISHMANIASIS; MAMMAL; NONHUMAN; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW; TRYPANOSOMA;

ANIMALS; ANTIPARASITIC AGENTS; BINDING SITES; ENZYME INHIBITORS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NADH, NADPH OXIDOREDUCTASES; PEPTIDES; POLYAMINES; SPECIES SPECIFICITY; SULFHYDRYL COMPOUNDS; TRYPANOSOMA;

LEISHMANIA DONOVANI; MAMMALIA; PROTOZOA; TRYPANOSOMA; VIOLA (ANGIOSPERM);

EID: 0037963699     PISSN: 09320113     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00436-002-0771-8     Document Type: Review

References (53)

1. Augustyns K, Amssoms K, Yamani A, Rajan PK, Haemers A (2001) Trypanothione as a target in the design of antitrypanosomal and antileishmanial agents. Curr Pharm Des 7:1117-1141
2. Austin SE, Khan MO, Douglas KT (1999) Rational drug design using trypanothione reductase as a target for anti-trypanosomal and anti-leishmanial drug leads. Drug Des Discov 16:5-23
3. Benson TJ, McKie JH, Garforth J, Borges A, Fairlamb AH, Douglas KT (1992) Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures. Biochem J 286:9-11
4. Blumenstiel K, Schöneck R, Yardley V, Croft SL, Krauth-Siegel RL (1999) Nitrofuran drugs as common subversive substrates of Trypanosoma cruzi lipoamide dehydrogenase and trypanothione reductase. Biochem Pharmacol 58:1791-1799
5. Bond CS, Zhang Y, Berriman M, Cunningham ML, Fairlamb AH, Hunter WN (1999) Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Struct Fold Des 7:81-89
6. Bonnet B, Soullez D, Davioud-Charvet E, Landry V, Horvath D, Sergheraert C (1997) New spermine and spermidine derivatives as potent inhibitors of Trypanosoma cruzi trypanothione reductase. Bioorg Med Chem 5:1249-1256
7. Bonse S, Krauth-Siegel RL, Schlichting I, Lowe G (1999a) Irreversible inhibitors of T. cruzi trypanothione reductase: kinetic and crystallographic studies. In: Ghisla S, Kroneck P, Macheroux P, Sund H (eds) Flavins and Ffavoproteins 1999. Rudolf Weber Agency, Berlin, pp 895-898
8. Bonse S, Santelli-Rouvier C, Barbe J, Krauth-Siegel RL (1999b) Inhibition of Trypanosoma cruzi trypanothione reductase by acridines: kinetic studies and structure-activity relationships. J Med Chem 42:5448-5454
9. Bonse S, Richards JM, Ross SA, Lowe G, Krauth-Siegel RL (2000) (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 43:4812-4821
10. Cenas N, Bironaite D, Dickancaite E, Anusevicius Z, Sarlauskas J, Blanchard JS (1994a) Chinifur, a selective inhibitor and "subversive substrate" for Trypanosoma congolense trypanothione reductase. Biochem Biophys Res Commun 204:224-229
11. Cenas NK, Arscott D, Williams CHJr, Blanchard JS (1994b) Mechanism of reduction of quinones by Trypanosoma congolense trypanothione reductase. Biochemistry 33:2509-2515
12. Chan C, Yin H, Garforth J, McKie JH, Jaouhari R, Speers P, Douglas KT, Rock PJ, Yardley V, Croft SL, Fairlamb AH (1998) Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs. J Med Chem 41:148-156
13. Chibale K, Haupt H, Kendrick H, Yardley V, Saravanamuthu A, Fairlamb AH, Croft SL (2001) Antiprotozoal and cytotoxicity evaluation of sulfonamide and urea analogues of quinacrine. Bioorg Med Chem Lett 11:2655-2657
14. Chitkul B, Bradley M (2000) Optimising inhibitors of trypanothione reductase using solid-phase chemistry. Bioorg Med Chem Lett 10:2367-2369
15. D'Silva C, Daunes S (2002) The therapeutic potential of inhibitors of the trypanothione cycle. Expert Opin Investig Drugs 11:217-231
16. Dumas C, Ouellette M, Tovar J, Cunningham ML, Fairlamb AH, Tamar S, Olivier M, Papadopoulou B (1997) Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. EMBO J 16:2590-2598
17. Faerman CH, Savvides SN, Strickland C, Breidenbach MA, Ponasik JA, Ganem B, Ripoll D, Krauth-Siegel RL, Karplus PA (1996) Charge is the major discriminating factor for glutathione reductase versus trypanothione reductase inhibitors. Bioorg Med Chem 4:1247-1253
18. Fairlamb AH, Cerami A (1992) Metabolism and functions of trypanothione in the Kinetoplastida. Annu Rev Microbiol 46:695-729
19. Fernandez-Gomez R, Moutiez M, Aumercier M, Bethegnies G, Luyckx M, Ouaissi A, Tartar A, Sergheraert C (1995) 2-Amino diphenylsulfides as new inhibitors of trypanothione reductase. Int J Antimicrob Agents 6:111-118
20. Fournet A, Inchausti A, Yaluff G, Rojas De Arias A, Guinaudeau H, Bruneton J, Breidenbach MA, Karplus PA, Faerman CH (1998) Trypanocidal bisbenzylisoquinoline alkaloids are inhibitors of trypanothione reductase. J Enzyme Inhib 13:1-9
21. Fournet A, Rojas de Arias A, Ferreira ME, Nakayama H, Torres de Ortiz S, Schinini A, Samudio M, Vera de Bilbao N, Lavault M, Bonte F (2000) Efficacy of the bisbenzylisoquinoline alkaloids in acute and chronic Trypanosoma cruzi murine model. Int J Antimicrob Agents 13:189-195
22. Gallwitz H, Bonse S, Martinez-Cruz A, Schlichting I, Schumacher K, Krauth-Siegel RL (1999) Ajoene is an inhibitor and subversive substrate of human glutathione reductase and Trypanosoma cruzi trypanothione reductase: crystallographic, kinetic, and spectroscopic studies. J Med Chem 42:364-372
23. Garforth J, Yin H, McKie JH, Douglas KT, Fairlamb AH (1997) Rational design of selective ligands for trypanothione reductase from Trypanosoma cruzi. Structural effects on the inhibition by dibenzazepines based on imipramine. J Enzyme Inhib 12:161-173
24. Garrard EA, Borman EC, Cook BN, Pike EJ, Alberg DG (2000) Inhibition of trypanothione reductase by substrate analogues. Org Lett 2:3639-3642
25. Girault S, Baillet S, Horvath D, Lucas V, Davioud-Charvet E, Tartar A, Sergheraert C (1997) New potent inhibitors of trypanothione reductase from Trypanosoma cruzi in the 2-aminodiphenylsulfide series. Eur J Med Chem 32:39-52
26. Girault S, Davioud-Charvet TE, Maes L, Dubremetz JF, Debreu MA, Landry V, Sergheraert C (2001) Potent and specific inhibitors of trypanothione reductase from Trypanosoma cruzi: bis(2-aminodiphenylsulfides) for fluorescent labeling studies. Bioorg Med Chem 9:837-846
27. Gutierrez-Correa J, Fairlamb AH, Stoppani AO (2001) Trypanosoma cruzi trypanothione reductase is inactivated by peroxidase-generated phenothiazine cationic radicals. Free Radic Res 34:363-378
28. Hammond DJ, Cover B, Gutteridge WE (1984) A novel series of chemical structures active in vitro against the trypomastigote form of Trypanosoma cruzi. Trans R Soc Trop Med Hyg 78:91-95
29. Henderson GB, Ulrich P, Fairlamb AH, Rosenberg I, Pereira M, Sela M, Cerami A (1988) "Subversive" substrates for the enzyme trypanothione disulfide reductase: alternative approach to chemotherapy of Chagas disease. Proc Natl Acad Sci U S A 85:5374-5378
30. Horvath D (1997) A virtual screening approach applied to the search for trypanothione reductase inhibitors. J Med Chem 40:2412-2423
31. Inhoff O, Richards JM, Brîet JW, Lowe G, Krauth-Siegel RL (2002) Coupling of a competitive and an irreversible ligand generates mixed type inhibitors of Trypanosoma cruzi trypanothione reductase. J Med Chem 45:4524-4530
32. Jacoby EM, Schlichting I, Lantwin CB, Kabsch W, Krauth-Siegel RL (1996) Crystal structure of the Trypanosoma cruzi trypanothione reductase mepacrine complex. Proteins 24:73-80
33. Jockers-Scherübl MC, Schirmer RH, Krauth-Siegel RL (1989) Trypanothione reductase from Trypanosoma cruzi. Catalytic properties of the enzyme and inhibition studies with trypanocidal compounds. Eur J Biochem 180:267-272
34. Khan MO, Austin SE, Chan C, Yin H, Marks D, Vaghjiani SN, Kendrick H, Yardley V, Croft SL, Douglas KT (2000) Use of an additional hydrophobic binding site, the Z site, in the rational drug design of a new class of stronger trypanothione reductase inhibitor, quaternary alkylammonium phenothiazines. J Med Chem 43:3148-3156
35. Krauth-Siegel RL, Coombs GH (1999) Enzymes of parasite thiol metabolism as drug targets. Parasitol Today 15:404-409
36. Krauth-Siegel RL, Jacoby EM, Jockers-Scherübl MC, Schlichting I, Barbe J (1997) T. cruzi trypanothione reductase: structure-function relationships of enzyme inhibitor complexes. In: Stevenson KJ, Massey V, Williams CHJr (eds) Flavins and flavoproteins 1996. University of Calgary Press, Calgary, pp 35-44
37. Krieger S, Schwarz W, Ariyanayagam MR, Fairlamb AH, KrauthSiegel RL, Clayton C (2000) Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Mol Microbiol 35:542-552
38. Li Z, Fennie MW, Ganem B, Hancock MT, Kobaslija M, Rattendi D, Bacchi CJ, O'Sullivan MC (2001) Polyamines with N-(3-phenylpropyl) substituents are effective competitive inhibitors of trypanothione reductase and trypanocidal agents. Bioorg Med Chem Lett 11:251-254
39. Lowe G, Droz AS, Vilaivan T, Weaver GW, Tweedale L, Pratt JM, Rock P, Yardley V, Croft SL (1999) Cytotoxicity of (2,2′:6′,2″-terpyridine)platinum(II) complexes to Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei. J Med Chem 42:999-1006
40. McKie JH, Garforth J, Jaouhari R, Chan C, Yin H, Besheya T, Fairlamb AH, Douglas KT (2001) Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate: potential rational drug design lead frameworks. Amino Acids 20:145-153
41. Moreno SN, Carnieri EG, Docampo R (1994) Inhibition of Trypanosoma cruzi trypanothione reductase by crystal violet. Mol Biochem Parasitol 67:313-320
42. Morrison J, Walsh CT (1988) The behaviour and significance of slow-binding enzyme inhibitors. Adv Enzymol Relat Areas Mol Biol 61:201-301
43. Obexer W, Schmid C, Barbe J, Galy JP, Brun R (1995) Activity and structure relationship of acridine derivatives against African trypanosomes. Trop Med Parasitol 46:49-53
44. O'Sullivan MC, Zhou Q, Li Z, Durham TB, Rattendi D, Lane S, Bacchi CJ (1997) Polyamine derivatives as inhibitors of trypanothione reductase and assessment of their trypanocidal activities. Bioorg Med Chem 5:2145-2155
45. Ponasik JA, Strickland C, Faerman C, Savvides S, Karplus PA, Ganem B (1995) Kukoamine A and other hydrophobic acylpolyamines: potent and selective inhibitors of Crithidia fasciculata trypanothione reductase. Biochem J 311:371-375
46. Rivarola HW, Fernandez AR, Enders JE, Fretes R, Gea S, Paglini-Oliva P (2001) Effects of clomipramine on Trypanosoma cruzi infection in mice. Trans R Soc Trop Med Hyg 95:529-533
47. Salmon-Chemin L, Buisine E, Yardley V, Kohler S, Debreu MA, Landry V, Sergheraert C, Croft SL, Krauth-Siegel RL, Davioud-Charvet E (2001) 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 44:548-565
48. Schirmer RH, Müller J, Krauth-Siegel RL (1995) Disulfide-reductase inhibitors as chemotherapeutic agents: the design of drugs for trypanosomiasis and malaria. Angew Chem Int Ed Engl 34:141-154
49. Schmidt A, Krauth-Siegel RL (2002) Enzymes of the trypanothione metabolism as targets for antitrypanosomal drug development. Curr Top Med Chem. Curr Top Med Chem 2:1239-1259
50. Smith HK, Bradley M (1999) Comparison of resin and solution screening methodologies in combinatorial chemistry and the identification of a 100 nM inhibitor of trypanothione reductase. J Comb Chem 1:326-332
51. Tovar J, Cunningham ML, Smith AC, Croft SL, Fairlamb AH (1998a) Down-regulation of Leishmania donovani trypanothione reductase by heterologous expression of a trans-dominant mutant homologue: effect on parasite intracellular survival. Proc Natl Acad Sci U S A 95:5311-5316
52. Tovar J, Wilkinson S, Mottram JC, Fairlamb AH (1998b) Evidence that trypanothione reductase is an essential enzyme in Leishmania by targeted replacement of the tryA gene locus. Mol Microbiol 29:653-660
53. Tromelin A, Moutiez M, Meziane-Cherif D, Aumercier M, Tartar A, Sergheraert C (1993) Synthesis of non reducible inhibitors for trypanothione reductase from Trypanosoma cruzi. Bioorg Med Chem 3:1971-1976