Assaying phenothiazine derivatives as trypanothione reductase and glutathione reductase inhibitors by theoretical docking and Molecular Dynamics studies

Journal of Molecular Graphics and Modelling

Volumn 28, Issue 4, 2009, Pages 371-381

  Iribarne, F ^a   Paulino, M ^a,b   Aguilera, S ^b   Tapia, O ^c  

^a UNIVERSIDAD DE LA REPÚBLICA   (Uruguay)

^b UNIVERSIDAD DE ANTOFAGASTA   (Chile)

^c UPPSALA UNIVERSITY   (Sweden)

Author keywords

Binding affinity; Chagas' disease; Molecular Dynamics; Phenothiazines; Theoretical docking; Trypanothione reductase

Indexed keywords

BINDING AFFINITY; CHAGAS' DISEASE; PHENOTHIAZINES; THEORETICAL DOCKING; TRYPANOTHIONE REDUCTASE;

BINDING SITES; CONFORMATIONS; DOCKING; DYNAMICS; ENZYME ACTIVITY; INSECTICIDES; LIGANDS; MOLECULAR DYNAMICS;

BINDING ENERGY;

ENZYME INHIBITOR; GLUTATHIONE REDUCTASE; LIGAND; PHENOTHIAZINE DERIVATIVE; PROMAZINE; TRYPANOTHIONE REDUCTASE;

ARTICLE; BINDING SITE; DRUG CONFORMATION; ELECTRICITY; ENERGY; ENZYME INHIBITION; ERYTHROCYTE; INHIBITION KINETICS; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR SIZE; PRIORITY JOURNAL; RECEPTOR AFFINITY; TRYPANOSOMA CRUZI; VALIDITY;

ANIMALS; BIOLOGICAL ASSAY; CATALYTIC DOMAIN; ENZYME INHIBITORS; GLUTATHIONE REDUCTASE; HUMANS; KINETICS; MOLECULAR DYNAMICS SIMULATION; NADH, NADPH OXIDOREDUCTASES; PARASITIC SENSITIVITY TESTS; PHENOTHIAZINES; PROTEIN STRUCTURE, SECONDARY; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; STATIC ELECTRICITY; THERMODYNAMICS; TRYPANOSOMA CRUZI;

TRYPANOSOMA CRUZI;

EID: 70350572363     PISSN: 10933263     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmgm.2009.09.003     Document Type: Article

References (75)

1. Rodrigues Coura J., and de Castro S.L. A critical review on Chagas disease chemotherapy. Mem. Inst. Oswaldo Cruz 97 1 (2002) 3-24
2. World Health Organization, Control of Chagas disease, Second Report of the WHO Expert Committee, Tech. Rep. Ser., vol. 905, 2002, pp. 1-109.
3. World Health Organization, Reporte de Grupo de Trabajo, 2007 (http://www.who.int/tdr/publications/tdr-research-publications/reporte-enfermedad-chagas/pdf/swg_chagas.pdf).
4. de Castro S.L. The challenge of Chagas disease chemotherapy: an update of drugs assayed against Trypansoma cruzi. Acta Trop. 53 2 (1993) 83-98
5. Soeiro M.N., and de Castro S.L. Trypanosoma cruzi targets for new chemotherapeutic approaches. Expert. Opin. Ther. Targets 13 1 (2009) 105-121
6. Dumas C., Ouellette M., Tovar J., Cunningham M.L., Fairlamb A.H., Tamar S., Olivier M., and Papadopoulou B. Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. EMBO J. 16 10 (1997) 2590-2598
7. Tovar J., Wilkinson S., Mottram J.C., and Fairlamb A.H. Evidence that trypanothione reductase is an essential enzyme in Leishmania by targeted replacement of the tryA gene locus. Mol. Microbiol. 29 2 (1998) 653-660
8. Tovar J., Cunningham M.L., Smith A.C., Croft S.L., and Fairlamb A.H. 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 9 (1998) 5311-5316
9. Krieger S., Schwarz W., Ariyanayagam M.R., Fairlamb A.H., Krauth-Siegel R.L., and Clayton C. Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Mol. Microbiol. 35 3 (2000) 542-552
10. Krauth-Siegel R.L., Meiering S.K., and Schmidt H. The parasite-specific trypanothione metabolism of trypanosoma and leishmania. Biol. Chem. 384 4 (2003) 539-549
11. Fairlamb A.H. Novel biochemical pathways in parasitic protozoa. Parasitology 99 Suppl. (1989) S93-S112
12. Fairlamb A.H. Future prospects for the chemotherapy of Chagas' disease. Medicina (Buenos Aires) 59 II (1999) 179-187
13. Nogoceke E., Gommel D.U., Kiess M., Kalisz H.M., and Flohe L.A. A unique cascade of oxidoreductases catalyses trypanothione-mediated peroxide metabolism in Crithidia fasciculate. Biol. Chem. 378 8 (1997) 827-836
14. Montemartini M., Nogoceke E., Gommel D.U., Singh M., Kalisz H.M., Steinert P., and Flohe L. Tryparedoxin and tryparedoxin peroxidase. Biofactors 11 1-2 (2000) 71-72
15. Hofmann B., Budde H., Bruns K., Guerrero S.A., Kalisz H.M., Menge U., Montemartini M., Nogoceke E., Steinert P., Wissing J.B., Flohe L., and Hecht H.J. Structures of tryparedoxins revealing interaction with trypanothione. Biol. Chem. 382 3 (2001) 459-471
16. Flohe L., Budde H., Bruns K., Castro H., Clos J., Hofmann B., Kansal-Kalavar S., Krumme D., Menge U., Plank-Schumacher K., Sztajer H., Wissing J., Wylegalla C., and Hecht H.J. Tryparedoxin peroxidase of Leishmania donovani: molecular cloning, heterologous expression, specificity, and catalytic mechanism. Arch. Biochem. Biophys. 397 2 (2002) 324-335
17. Shames S.L., Fairlamb A.H., Cerami A., and Walsh C.T. Purification and characterization of trypanothione reductase from Crithidia fasciculata, a newly discovered member of the family of disulfide-containing flavoprotein reductases. Biochemistry 25 12 (1986) 3519-3526
18. Krauth-Siegel R.L., Enders B., Henderson G.B., Fairlamb A.H., and Schirmer R.H. Trypanothione reductase from Trypanosoma cruzi. Purification and characterization of the crystalline enzyme. Eur. J. Biochem. 164 1 (1987) 123-128
19. Ghisla S., and Massey V. Mechanisms of flavoprotein-catalyzed reactions. Eur. J. Biochem. 181 1 (1989) 1-17
20. Karplus P.A., and Schulz G.E. Substrate binding and catalysis by glutathione reductase as derived from refined enzyme: substrate crystal structures at 2 A resolution. J. Mol. Biol. 210 1 (1989) 163-180
21. Hunter W.N., Smith K., Derewenda Z., Harrop S.J., Habash J., Islam M.S., Helliwell J.R., and Fairlamb A.H. Initiating a crystallographic study of trypanothione reductase. J. Mol. Biol. 216 2 (1990) 235-237
22. Bond C.S., Zhang Y., Berriman M., Cunningham M.L., Fairlamb A.H., and 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 7 1 (1999) 81-89
23. Díaz W., Aullo J.M., Paulino M., and Tapia O. Transition structure and reactive complexes for hydride transfer in an isoalloxazine-nicotinamide complex. On the catalytic mechanism of glutathione reductase. An ab initio MO SCF study. Chem. Phys. 204 2-3 (1996) 195-203
24. Iribarne F., Paulino M., and Tapia O. Hydride-transfer transition structure as a possible unifying redox step for describing the branched mechanism of glutathione reductase. Molecular-electronic antecedents. Theor. Chem. Acc. 103 6 (2000) 451-462
25. Grinblat L., Sreider C.M., and Stoppani A.O.M. Nitrofuran inhibition of yeast and rat tissue glutathione reductases. Structure-activity relationships. Biochem. Pharmacol. 38 5 (1989) 767-772
26. Paulino M., Iribarne F., Dubin M., Aguilera-Morales S., Tapia O., and Stoppani A.O. The chemotherapy of Chagas' disease: an overview. Mini. Rev. Med. Chem. 5 5 (2005) 499-519
27. V.G. Duschak, A.S. Couto, An insight on targets and patented drugs for chemotherapy of Chagas disease, Recent Patents on Anti-Infective Drug Discovery, vol. 2, no. 1, 2007, pp. 19-51.
28. Cerecetto H., and Gonzalez M. Anti-T. cruzi agents: our experience in the evaluation of more than five hundred compounds. Mini Rev. Med. Chem. 8 13 (2008) 1355-1383
29. Pearson R.D., Manian A.A., Harcus J.L., Hall D., and Hewlett E.L. Lethal effect of phenothiazine neuroleptics on the pathogenic protozoan Leishmania donovani. Science 217 4557 (1982) 369-371
30. Pearson R.D., Manian A.A., Hall D., Harens J., and Hewlett E.L. Antileishmanial activity of chlorpromazine. Antimicrob. Agents Chemother. 25 5 (1984) 571-574
31. Seebeck T., and Gehr P. Trypanocidal action of neuroleptic phenothiazines in Trypanosoma brucei. Mol. Biochem. Parasitol. 9 3 (1983) 197-208
32. Zilberstein D., and Dwyer D.M. Antidepressants cause lethal disruption of membrane function in the human protozoan parasite Leishmania. Science 226 4677 (1984) 977-979
33. Hewlett E.L., Pearson R.D., Zilberstein D., and Dwyer D.M. Antiprotozoal activity of tricyclic compounds. Science 230 4729 (1985) 1063-1064
34. Hammond D.J., Cover B., and 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. 78 1 (1984) 91-95
35. Hammond D.J., Hogg J., and Gutteridge W.E. Trypanosoma cruzi: possible control of parasite transmission by blood transfusion using amphiphilic cationic drugs. Exp. Parasitol. 60 1 (1985) 32-42
36. Stieger J., and Seebeck T. Monoclonal antibodies against a 60 kDa phenothiazine-binding protein from Trypanosoma brucei can discriminate between different trypanosome species. Mol. Biochem. Parasitol. 21 1 (1986) 37-45
37. Croft S.L., Walker J.J., and Gutteridge W.E. Screening of drugs for rapid activity against Trypanosoma cruzi trypomastigotes in vitro. Trop. Med. Parasitol. 39 2 (1988) 145-148
38. Doyle P.S., and Weinbach E.C. The activity of tricyclic antidepressant drugs against Trypanosoma cruzi. Exp. Parasitol. 68 2 (1989) 230-234
39. Benson T.J., McKie J.H., Garforth J., Borges A., Fairlamb A.H., and Douglas K.T. Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures. J. Biochem. 286 Pt. 1 (1992) 9-11
40. Chan C., Yin H., Garforth J., McKie J.H., Jaouhari R., Speers P., Douglas K.T., Rock P.J., Yardley V., Croft S.L., and Fairlamb A.H. Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs. J. Med. Chem. 41 24 (1998) 148-156
41. Gutierrez-Correa J., Fairlamb A.H., and Stoppani A.O.M. Trypanosoma cruzi trypanothione reductase is inactivated by peroxidase-generated phenothiazine cationic radicals. Free Radic. Res. Commun. 34 4 (2001) 363-378
42. Gutierrez-Correa J., and Stoppani A.O.M. Myeloperoxidase-generated phenothiazine cation radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase. Rev. Argen. Microbiol. 34 2 (2002) 83-94
43. Tapia O., Paulino M., and Stamato F.M.L.G. Computer assisted simulations and molecular graphics methods in molecular design. 1. Theory and applications to enzyme active-site directed drug design. Mol. Eng. 3 (1994) 377-414
44. Kuntz I.D. Structure-based strategies for drug design and discovery. Science 257 5073 (1992) 1078-1082
45. Kuntz I.D., Meng E.C., and Shoichet B.K. Structure-based molecular design. Acc. Chem. Res. 27 5 (1994) 117-123
46. Muegge I., and Rarey M. In: Lipkowitz K.B., and Boyd D.B. (Eds). Small Molecule Docking and Scoring. Reviews in Computational Chemistry vol. 17 (2001), VCH Publishers, New York 1-60
47. Cummings M.D., DesJarlais R.L., Gibbs A.C., Mohan V., and Jaeger E.P. Comparison of automated docking programs as virtual screening tools. J. Med. Chem. 48 4 (2005) 962-976
48. Kontoyianni M., Madhav P., Suchanek E., and Seibel W. Theoretical and practical considerations in virtual screening: a beaten field?. Curr. Med. Chem. 15 2 (2008) 107-116
49. Ferrara P., Priestle J.P., Vangrevelinghe E., and Jacoby E. New developments and applications of docking and high-throughput docking for drug design and in silico screening. Curr. Comp.-Aided Drug Des. 2 1 (2006) 83-91
50. Iribarne F., Paulino M., Gonzalez M., Cerecetto H., Aguilera S., and Tapia O. Interaction energies of nitrofuran with glutatione and trypanothione reductase studied by molecular docking. J. Mol. Struct. (TEOCHEM) 818 1-3 (2007) 7-22
51. Paulino M., Iribarne F., Hansz M., Vega M., Seoane G., Cerecetto H., Di Maio R., Caracelli I., Zuckerman-Schpector J., Olea C., Stoppani A.O.M., Basombrío M.A., Berriman M., Fairlamb A.H., and Tapia O. Computer assisted design of potentially active anti-trypanosomal compounds. J. Mol. Struct. (TEOCHEM) 584 (2002) 95-105
52. Stewart J.J.P. Optimization of paramters for semi-empirical methods I. Method. J. Comp. Chem. 10 2 (1989) 209-220
53. Schmidt M.W., Baldridge K.K., Boatz J.A., Elbert S.T., Gordon M.S., Jensen J.H., Koseki S., Matsunaga N., Nguyen K.A., Su S., Windus T.L., Dupuis M., and Montgomery J.A. General atomic and molecular electronic structure system. J. Comput. Chem. 14 11 (1993) 1347-1363
54. Becke A.D. Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev. A 38 6 (1988) 3098-3100
55. Becke A.D. A new mixing of Hartree-Fock and local density-functional theories. J. Chem. Phys. 98 2 (1993) 1372-1377
56. Becke A.D. Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 98 7 (1993) 5648-5652
57. Humphrey W., Dalke A., and Schulten K. VMD: visual molecular dynamics. J. Mol. Graph. 14 1 (1996) 33-38
58. Jones T.A., and Kjeldgaard M. Manual for O (1990), Uppsala University
59. van Gunsteren W.F., Billeter S.R., Eising A.A., Hunenberger P.H., Kruger P., Mark A.E., Scott W.R.P., and Tironi I.G. In: Biomos B.V. (Ed). Biomolecular Simulation: The GROMOS96 Manual and User Guide (1996), Zurich Groningen, Switzerland
60. Cramer III R.D., Patterson D.E., and Bunce J.D. Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc. 11 (1988) 5959-5967
61. Tripos Inc. Sybyl 6. 8 (2001), Tripos, St. Louis
62. Silva G.M., Sant'Anna C.M., and Barreiro E.J. A novel 3D-QSAR comparative molecular field analysis (CoMFA) model of imidazole and quinazolinone functionalized p38 MAP kinase inhibitors. Bioorg. Med. Chem. 12 12 (2004) 3159-3166
63. Khan M.O.F., Austin S.E., Chan C., Yin H., Marks D., Vaghjiani S., Kendrick H., Yardley V., Croft S.L., and Douglas K.T. 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 16 (2000) 3148-3156
64. Holloway G.A., Baell J.B., Fairlamb A.H., Novello P.M., Parisot J.P., Richardson J., Watson K.G., and Street I.P. Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening. Bioorg. Med. Chem. Lett. 17 5 (2007) 1422-1427
65. Faerman C.H., Savvides S.N., Strickland C., Breidenbach M.A., Ponasik J.A., Ganem B., Ripoll D., Krauth-Siegel R.L., and Karplus P.A. Charge is the major discriminating factor for glutathione reductase versus trypanothione reductase inhibitors. Bioorg. Med. Chem. 4 8 (1996) 1247-1253
66. Bonse S., Santelli-Rouvier C., Barbe J., and Krauth-Siegel R.L. Inhibition of Trypanosoma cruzi trypanothione reductase by acridines: kinetic studies and structure-activity relationships. J. Med. Chem. 42 26 (1999) 5448-5454
67. Parveen S., Khan M.O., Austin S.E., Croft S.L., Yardley V., Rock P., and Douglas K.T. Antitrypanosomal, antileishmanial, and antimalarial activities of quaternary arylalkylammonium 2-amino-4-chlorophenyl phenyl sulfides, a new class of trypanothione reductase inhibitor, and of N-acyl derivatives of 2-amino-4-chlorophenyl phenyl sulfide. J. Med. Chem. 48 25 (2005) 8087-8097
68. Martyn D.C., Jones D.C., Fairlamb A., and Clardy H. High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity. J. Bioorg. Med. Chem. Lett. 17 5 (2007) 1280-1283
69. Stump B., Eberle C., Kaiser M., Brun R., Krauth-Siegel R.L., and Diederich F. Diaryl sulfide-based inhibitors of trypanothione reductase: inhibition potency, revised binding mode and antiprotozoal activities. Org. Biomol. Chem. 6 21 (2008) 3935-3947
70. Austin S.E., Khan M.O.F., and Douglas K.T. Rational drug design using trypanothione reductase as a target for anti-trypanosomal and anti-leishmanial drug leads. Drug Des. Discov. 16 1 (1999) 5-23
71. Iribarne F., Paulino M., Aguilera S., Murphy M., and Tapia O. Docking and molecular dynamics studies at trypanothione reductase and glutathione reductase active sites. J. Mol. Model. 8 5 (2002) 173-183
72. Fernández A.R., Fretes R., Rubiales S., Lacuara J.L., and Paglini-Oliva P. Trypanocidal effects of promethazine. Medicina (Buenos Aires) 57 1 (1997) 59-63
73. Rivarola H.W., Fernández A.R., Enders J.E., Fretes R., Gea S., Suligoy M., Palma J.A., and Paglini-Oliva P. Thioridazine treatment modifies the evolution of Trypanosoma cruzi infection in mice. Ann. Trop. Med. Parasitol. 93 7 (1999) 695-702
74. Rivarola H.W., and Paglini-Oliva P.A. Trypanosoma cruzi trypanothione reductase inhibitors: phenothiazines and related compounds modify experimental Chagas' disease evolution. Curr. Drug Targets Cardiovasc. Haematol. Disord. 2 1 (2002) 43-52
75. Lo Presti M.S., Rivarola H.W., Bustamante J.M., Fernández A.R., Enders J.E., Fretes R., Gea S., and Paglini-Oliva P.A. Thioridazine treatment prevents cardiopathy in Trypanosoma cruzi infected mice. Int. J. Antimicrob. Agents 23 6 (2004) 634-636