Redox-Active Agents in Reactions Involving the Trypanothione/Trypanothione Reductase-based System to Fight Kinetoplastidal Parasites

Gendron, Thibault; Lanfranchi, Don Antoine; Davioud-Charvet, Elisabeth

doi:10.1002/9783527670383.ch22

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Redox-Active Agents in Reactions Involving the Trypanothione/Trypanothione Reductase-based System to Fight Kinetoplastidal Parasites

Gendron, Thibault; Lanfranchi, Don Antoine; Davioud-Charvet, Elisabeth

2013 • In Trypanosomatid Diseases: Molecular Routes to Drug Discovery

Editorial reviewed

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https://hdl.handle.net/2268/297334

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10.1002/9783527670383.ch22

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Keywords :

Drug development; Flavoenzyme; Kinetoplastids; NADPH; Redox-active agent; Subversive substrate; Trypanothione; Trypanothione reductase; Medicine (all); Pharmacology, Toxicology and Pharmaceutics (all)

Abstract :

[en] African trypanosomiasis, Chagas disease, and leishmaniasis are human infectious diseases caused by various kinetoplastid parasites. Trypanothione reductase (TR) is a flavoenzyme unique to these parasites that is responsible for maintaining trypanothione (bis(glutathionyl)spermidine) in its reduced dithiol form. This enzyme plays a crucial role in the thiol redox metabolism and is essential in vivo for all trypanosomatids living in the human host studied so far. These findings make the flavoenzyme a promising target for anti-kinetoplastidal drug development. In this chapter, we examine the work published in the field of redox-active agents acting as substrates of the NADPH-dependent TR-based system. We also highlight our own work on trypanothione-reactive agents and discuss how these compounds might be developed as potential specific lead compounds to fight kinetoplastidal parasites. © 2013 Wiley-VCH Verlag GmbH & Co. KGaA.

Disciplines :

Chemistry
Immunology & infectious disease

Author, co-author :

Gendron, Thibault ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique-nucléaire ; UMR CNRS 7509, European School of Chemistry, Polymers and Materials (ECPM), 67087 Strasbourg Cedex 2, France

Lanfranchi, Don Antoine; UMR CNRS 7509, European School of Chemistry, Polymers and Materials (ECPM), 67087 Strasbourg Cedex 2, France

Davioud-Charvet, Elisabeth; UMR CNRS 7509, European School of Chemistry, Polymers and Materials (ECPM), 67087 Strasbourg Cedex 2, France

Language :

English

Title :

Redox-Active Agents in Reactions Involving the Trypanothione/Trypanothione Reductase-based System to Fight Kinetoplastidal Parasites

Publication date :

04 April 2013

Main work title :

Trypanosomatid Diseases: Molecular Routes to Drug Discovery

Publisher :

Wiley-VCH

ISBN/EAN :

978-3-527-33255-7

Peer reviewed :

Editorial reviewed

Additional URL :

https://onlinelibrary.wiley.com/doi/pdf/10.1002/9783527670383.ch22

Available on ORBi :

since 14 December 2022

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Bibliography

Schirmer, R.H., Müller, J.G., and Krauth-Siegel, R.L. (1995) Disulfide-reductase inhibitors as chemotherapeutic agents: the design of drugs for Trypanosomiasis and Malaria. Angew. Chem. Int. Ed. Engl., 34, 141-154.
Krauth-Siegel, R.L., Bauer, H., and Schirmer, R.H. (2005) Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia. Angew. Chem. Int. Ed., 44, 690-715.
Williams, C.H.J. (1991) Lipoamide dehydrogenase, glutathione reductase, thioredoxin reductase, and mercuric ion reductase - a family of flavoenzyme transhydrogenases, in Chemistry and Biochemistry of Flavoenzymes (ed. F. Müller), CRC Press, Boca Raton, FL, vol. III, pp. 121-211.
Argyrou, A. and Blanchard, J. (2004) Flavoprotein disulfide reductases: advances in chemistry and function. Prog. Nucleic Acid Res. Mol. Biol., 78, 89-142.
Fairlamb, A., Blackburn, P., Ulrich, P., Chait, B., and Cerami, A. (1985) Trypanothione: a novel bis(glutathionyl) spermidine cofactor for glutathione reductase in trypanosomatids. Science, 227, 1485-1487.
Fairlamb, A., Henderson, G., and Cerami, A. (1986) The biosynthesis of trypanothione and N1-glutathionylspermidine in Crithidia fasciculata. Mol. Biochem. Parasitol., 21, 247-257.
Shames, S.L., Fairlamb, A.H., Cerami, A., and Walsh, C.T. (1986) Purification and characterization of trypanothione reductase from Crithidia fasciculata, a new member of the family of disulfidecontaining flavoprotein reductases. Biochemistry, 25, 3519-3526.
Montrichard, F., Le Guen, F., Laval-Martin, D.L., and Davioud-Charvet, E. (1999) Evidence for the co-existence of glutathione reductase and trypanothione reductase in the non-trypanosomatid Euglenozoa: Euglena gracilis Z. FEBS Lett., 442, 29-33.
Schirmer, R.H., Schöllhammer, T., Eisenbrand, G., and Krauth-Siegel, R.L. (1987) Oxidative stress as a defense mechanism against parasitic infections. Free Radic. Res., 3, 3-12.
Schmidt, H. and Krauth-Siegel, R.L. (2003) Functional and physicochemical characterization of the thioredoxin system in Trypanosoma brucei. J. Biol. Chem., 278, 46329-46336.
Bond, C.S., Zhang, Y., Berriman, M., Cunningham, M.L., Fairlamb, A.H., and Hunter, W.N. (1999) Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure, 7, 81-89.
Salmon-Chemin, L., Buisine, E., Yardley, V., Kohler, S., Debreu, M.-A., Landry, V., Sergheraert, C. et al. (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.
Vega-Teijido, M., Caracelli, I., and Zukerman-Schpector, J. (2006) Conformational analyses and docking studies of a series of 5-nitrofuran- and 5-nitrothiophen-semicarbazone derivatives in three possible binding sites of trypanothione and glutathione reductases. J. Mol. Graph. Model., 24, 349-355.
Iribarne, F., González, M., Cerecetto, H., Aguilera, S., Tapia, O., and Paulino, M. (2007) Interaction energies of nitrofurans with trypanothione reductase and glutathione reductase studied by molecular docking. J. Mol. Struct., 818, 7-22.
Stump, B., Kaiser, M., Brun, R., Krauth-Siegel, R.L., and Diederich, F. (2007) Betraying the parasite's redox system: diaryl sulfide-based inhibitors of trypanothione reductase: subversive substrates and antitrypanosomal properties. ChemMedChem, 2, 1708-1712.
Faerman, C.H., Savvides, S.N., Strickland, C., Breidenbach, M.A., Ponasik, J.A., Ganem, B., Ripoll, D. et al. (1996) Charge is the major discriminating factor for glutathione reductase versus trypanothione reductase inhibitors. Bioorg. Med. Chem., 4, 1247-1253.
Jacoby, E.M., Schlichting, I., Lantwin, C.B., Kabsch,W., and Krauth-Siegel, R.L. (1996) Crystal structure of the Trypanosoma cruzi trypanothione reductase·mepacrine complex. Proteins, 24, 73-80.
Khan, M.O.F., Austin, S.E., Chan, C., Yin, H., Marks, D., Vaghjiani, S.N., Kendrick, H. et al. (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.
Aguirre, G., Cabrera, E., Cerecetto, H., Di Maio, R., González, M., Seoane, G., Duffaut, A. et al. (2004) Design, synthesis and biological evaluation of new potent 5-nitrofuryl derivatives as anti-Trypanosoma cruzi agents. Studies of trypanothione binding site of trypanothione reductase as target for rational design. Eur. J. Med. Chem., 39, 421-431.
Wyllie, S., Cunningham, M.L., and Fairlamb, A.H. (2004) Dual action of antimonial drugs on thiol redox metabolism in the human pathogen leishmania donovani. J. Biol. Chem., 279, 39925-39932.
Dumas, C., Ouellette, M., Tovar, J., Cunningham, M.L., Fairlamb, A.H., Tamar, S., Olivier, M. et al. (1997) Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. EMBO J., 16, 2590-2598.
Krieger, S., Schwarz,W., Ariyanayagam, M.R., Fairlamb, A.H., Krauth-Siegel, R.L., and Clayton, C. (2000) Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Mol. Microbiol., 35, 542-552.
Davioud-Charvet, E., Becker, K., Landry, V., Gromer, S., Logé, C., and Sergheraert, C. (1999) Synthesis of 5,50-dithiobis(2-nitrobenzamides)as alternative substrates for trypanothione reductase and thioredoxin reductase: a microtiter colorimetric assay for inhibitor screening. Anal. Biochem., 268, 1-8.
Hamilton, C.J., Saravanamuthu, A., Eggleston, I.M., and Fairlamb, A.H. (2003) Ellman's-reagent-mediated regeneration of trypanothione in situ: substrate-economical microplate and time-dependent inhibition assays for trypanothione reductase. Biochem. J., 369, 529-537.
Müller, T., Johann, L., Jannack, B., Brückner, M., Lanfranchi, D.A., Bauer, H., Sanchez, C. et al. (2011) Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones - a new strategy to combat malarial parasites. J. Am. Chem. Soc., 133, 11557-11571.
Davioud-Charvet, E. and Lanfranchi, D.A. (2011) Subversive substrates of glutathione reductases from Plasmodium falciparuminfected red blood cells as antimalarial agents, in Apicomplexan Parasites (ed. K. Becker), Wiley-VCH Verlag GmbH, Weinheim, pp 373-396.
Johann, L., Lanfranchi, D.A., Davioud-Charvet, E., and Elhabiri, M. (2012) A physico-biochemical study with redoxcyclers as antimalarial and antischistosomal drugs. Curr. Pharm. Des., 18, 3539-3566.
Blank, O., Davioud-Charvet, E., and Elhabiri, M. (2012) Interactions of the antimalarial drug methylene blue with methemoglobin and heme targets in plasmodium falciparum: a physicobiochemical study. Antioxid. Redox Signal., 17, 544-554.
Henderson, G.B., Ulrich, P., Fairlamb, A.H., Rosenberg, I., Pereira, M., Sela, M., and Cerami, A. (1988) 'Subversive' substrates for the enzyme trypanothione disulfide reductase: alternative approach to chemotherapy of Chagas disease. Proc. Natl. Acad. Sci. USA, 85, 5374-5378.
Blumenstiel, K., Schöneck, R., Yardley, V., Croft, S.L., and Krauth-Siegel, R.L. (1999) Nitrofuran drugs as common subversive substrates of Trypanosoma cruzi lipoamide dehydrogenase and trypanothione reductase. Biochem. Pharmacol., 58, 1791-1799.
Salmon-Chemin, L., Lemaire, A., De Freitas, S., Deprez, B., Sergheraert, C., and Davioud-Charvet, E. (2000) Parallel synthesis of a library of 1,4-naphthoquinones and automated screening of potential inhibitors of trypanothione reductase from Trypanosoma cruzi. Bioorg. Med. Chem. Lett., 10, 631-635.
Biot, C., Bauer, H., Schirmer, R.H., and Davioud-Charvet, E. (2004) 5-substituted tetrazoles as bioisosteres of carboxylic acids. Bioisosterism and mechanistic studies on glutathione reductase inhibitors as antimalarials. J. Med. Chem., 47, 5972-5983.
Krauth-Siegel, R.L. and Davioud-Charvet, E. (2005) Trypanothione reductase and other flavoenzymes as targets of antiparasitic drugs, in Flavins and Flavoproteins 2005 (eds T. Nishino, R. Miura, M. Tanokura, and K. Fukui), ARchiTect, Tokyo, pp 867-876.
Bauer, H., Fritz-Wolf, K., Winzer, A., Kühner, S., Little, S., Yardley, V., Vezin, H. et al. (2006) A fluoro analogue of the menadione derivative 6-[20-(30-methyl)-1040-naphthoquinolyl]hexanoic acid is a suicide substrate of glutathione reductase. Crystal structure of the alkylated human enzyme. J. Am. Chem. Soc., 128, 10784-10794.
Morin, C., Besset, T., Moutet, J.-C., Fayolle, M., Brückner, M., Limosin, D., Becker, K. et al. (2008) The aza-analogues of 1,4-naphthoquinones are potent substrates and inhibitors of plasmodial thioredoxin and glutathione reductases and of human erythrocyte glutathione reductase. Org. Biomol. Chem., 6, 2731-2742.
Lanfranchi, D.A., Belorgey, D., Müller, T., Vezin, H., Lanzer, M., and Davioud-Charvet, E. (2012) Exploring the trifluoromenadione core as a template to design antimalarial redox-active agents interacting with glutathione reductase. Org. Biomol. Chem., 10, 4795-4806.
Pai, E.F., Karplus, P.A., and Schulz, G.E. (1988) Crystallographic analysis of the binding of NADPH, NADPH fragments, and NADPH analogues to glutathione reductase. Biochemistry, 27, 4465-4474.
Karplus, P.A. and Schulz, G.E. (1987) Refined structure of glutathione reductase at 1.54A_ resolution. J. Mol. Biol., 195, 701-729.
Karplus, P.A., Pai, E.F., and Schulz, G.E. (1989) A crystallographic study of the glutathione binding site of glutathione reductase at 0.3-nm resolution. Eur. J. Biochem., 178, 693-703.
Cenas, N.K., Arscott, D., Williams, C.H., and Blanchard, J.S. (1994) Mechanism of reduction of quinones by Trypanosoma congolense trypanothione reductase. Biochemistry, 33, 2509-2515.
Cornish-Bowden, A. (1986) Why is uncompetitive inhibition so rare? FEBS Lett., 203, 3-6.
Apted, F.I.C. (1960) Nitrofurazone in the treatment of sleeping sickness due to Trypanosoma rhodesiense. Trans. R. Soc. Trop. Med. Hyg., 54, 225-228.
Simarro, P.P., Diarra, A., Ruiz Postigo, J.A., Franco, J.R., and Jannin, J.G. (2011) The Human African Trypanosomiasis Control and Surveillance Programme of the World Health Organization 2000-2009: The Way Forward. PLoS Negl. Trop. Dis., 5, e1007.
Sokolova, A.Y., Wyllie, S., Patterson, S., Oza, S.L., Read, K.D., and Fairlamb, A.H. (2010) Cross-resistance to nitro drugs and implications for treatment of human African trypanosomiasis. Antimicrob. Agents Chemother., 54, 2893-2900.
Cenas, N., Bironaite, D., Dickancaite, E., Anusevicius, Z., Sarlauskas, J., and Blanchard, J.S. (1994) Chinifur, a selective inhibitor and 'subversive substrate' for Trypanosoma congolense trypanothione reductase. Biochem. Biophys. Res. Commun., 204, 224-229.
Maya, J.D., Bollo, S., Nuñez-Vergara, L.J., Squella, J.A., Repetto, Y., Morello, A., Périé, J. et al. (2003) Trypanosoma cruzi: effect and mode of action of nitroimidazole and nitrofuran derivatives. Biochem. Pharmacol., 65, 999-1006.
Julião, M.S., da, S., Ferreira, E.I., Ferreira, N.G., and Serrano, S.H.P. (2006) Voltammetric detection of the interactions between RNO2_ and electron acceptors in aqueous medium at highly boron doped diamond electrode (HBDDE). Electrochim. Acta, 51, 5080-5086.
Hall, B.S., Bot, C., and Wilkinson, S.R. (2011) Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites. J. Biol. Chem., 286, 13088-13095.
Carter, N.S. and Fairlamb, A.H. (1993) Arsenical-resistant trypanosomes lack an unusual adenosine transporter. Nature, 361, 173-176.
Stewart, M.L., Bueno, G.J., Baliani, A., Klenke, B., Brun, R., Brock, J.M., Gilbert, I.H. et al. (2004) Trypanocidal activity of melamine-based nitroheterocycles. Antimicrob. Agents Chemother., 48, 1733-1738.
Baliani, A., Peal, V., Gros, L., Brun, R., Kaiser, M., Barrett, M.P., and Gilbert, I.H. (2009) Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites. Org. Biomol. Chem., 7, 1154.
Chung, M.-C., Güido, R.V.C., Martinelli, T.F., GonScalves, M.F., Polli, M.C., Botelho, K.C.A., Varanda, E.A. et al. (2003) Synthesis and in vitro evaluation of potential antichagasic hydroxymethylnitrofurazone (NFOH-121): a new nitrofurazone prodrug. Bioorg. Med. Chem., 11, 4779-4783.
Davies, C., Cardozo, R.M., Negrette, O.S., Mora, M.C., Chung, M.C., and Basombrio, M.A. (2010) Hydroxymethylnitrofurazone is active in a murine model of Chagas disease. Antimicrob. Agents Chemother., 54, 3584-3589.
Fotie, J., Kaiser, M., Delfiín, D.A., Manley, J., Reid, C.S., Paris, J.-M., Wenzler, T. et al. (2010) Antitrypanosomal activity of 1,2-dihydroquinolin-6-ols and their ester derivatives. J. Med. Chem., 53, 966-982.
Schirmer, R.H., Adler, H., Pickhardt, M., and Mandelkow, E. (2011) 'Lest we forget you-methylene blue. '. Neurobiol. Aging, 32, 2325.e7-2325.e16.
Boda, C., Enanga, B., Courtioux, B., Breton, J.-C., and Bouteille, B. (2006) Trypanocidal activity of methylene blue. Chemotherapy, 52, 16-19.
Buchholz, K., Comini, M.A., Wissenbach, D., Schirmer, R.H., Krauth-Siegel, R.L., and Gromer, S. (2008) Cytotoxic interactions of methylene blue with trypanosomatid-specific disulfide reductases and their dithiol products. Mol. Biochem. Parasitol., 160, 65-69.
Sukhova, N.M., Lidaka, M.J., Voronova, V.A., Zidermane, A.A., Kravchenko, I.M., Dauvarte, A.Z., Preisa, I.E. et al. (1979) amides substitu_es d'acides 20-(20-(500nitrofuranyl-200)vinyl et 4-(500-nitrofuranyl-200)-1,3-butadienyl)quinoléine-4-carboxyliques, leur procédé de préparation et leur application thérapeutique. French Patent FR19780026058.
Fernandez-Gomez, R., Moutiez, M., Aumercier, M., Bethegnies, G., Luyckx, M., Ouaissi, A., Tartar, A. et al. (1995) 2-Amino diphenylsulfides as new inhibitors of trypanothione reductase. Int. J. Antimicrob. Agents, 6, 111-118.
Davioud-Charvet, E., McLeish, M.J., Veine, D., Giegel, D., Andricopulo, A.D., Becker, K., and Müller, S. (2002) Mechanism-based inactivation of thioredoxin reductase from Plasmodium falciparum by Mannich bases. Implications for drug design, in Flavins and Flavoproteins 2002 (eds S. Chapman, R. Perham, and N. Scrutton), Weber, Berlin, pp 845-851.
Davioud-Charvet, E., McLeish, M.J., Veine, D.M., Giegel, D., Arscott, L.D., Andricopulo, A.D., Becker, K. et al. (2003) Mechanism-based inactivation of thioredoxin reductase from Plasmodium falciparum by Mannich bases. Implication for cytotoxicity. Biochemistry, 42, 13319-13330.
Lee, B., Bauer, H., Melchers, J., Ruppert, T., Rattray, L., Yardley, V., Davioud-Charvet, E. et al. (2005) Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate. J. Med. Chem., 48, 7400-7410.
Wenzel, I.N., Wong, P.E., Maes, L., Müller, T.J.J., Krauth-Siegel, R.L., Barrett, M.P., and Davioud-Charvet, E. (2009) Unsaturated Mannich bases active against multidrug-resistant Trypanosoma brucei brucei strains. ChemMedChem, 4, 339-351.
Angiolini, L., Ghedini, N., and Tramontini, M. (1985) The Mannich bases in polymer synthesis. 10. Synthesis of poly (b-ketothioethers) and their behaviour towards hydroperoxide reagents. Polymer Commun., 26, 218-221.
Wyllie, S., Patterson, S., Stojanovski, L., Simeons, F.R.C., Norval, S., Kime, R., Read, K.D. et al. (2012) The antitrypanosome drug fexinidazole shows potential for treating visceral leishmaniasis. Sci. Transl. Med., 4, 119re1-119re1.
Capes, A., Patterson, S., Wyllie, S., Hallyburton, I., Collie, I.T., McCarroll, A.J., Stevens, M.F.G. et al. (2012) Quinol derivatives as potential trypanocidal agents. Bioorg. Med. Chem., 20, 1607-1615.