A critical review on chagas disease chemotherapy

Memorias do Instituto Oswaldo Cruz

Volumn 97, Issue 1, 2002, Pages 3-24

  Coura, José Rodrigues ^a   De Castro, Solange L ^a  

^a INSTITUTO OSWALDO CRUZ   (Brazil)

Author keywords

Chagas disease; Chemotherapy; Clinical treatment; Drug development; Review; Trypanosoma cruzi

Indexed keywords

ANTITRYPANOSOMAL AGENT; BENZNIDAZOLE; NIFURTIMOX; NITROIMIDAZOLE DERIVATIVE;

CHAGAS DISEASE; HUMAN; REVIEW;

CHAGAS DISEASE; HUMANS; NIFURTIMOX; NITROIMIDAZOLES; TRYPANOCIDAL AGENTS;

EID: 0036359943     PISSN: 00740276     EISSN: None     Source Type: Journal    
DOI: 10.1590/S0074-02762002000100001     Document Type: Review

References (279)

1. Alves TM, Alves R, Romanha AJ, Zani CL, Dos Santos MH, Nagem TJ 1999. Biological activities of 7-epiclusianone. J Nat Prod 62: 369-371.
2. Andrade AL, Zicker F, de OliveiraRM, Almeida Silva S, Luquetti A, Travassos LR, Almeida IC, De Andrade SS, de Andrade JG, Martelli CM 1996. Randomized trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet 348: 1407-1413.
3. Andrade SG, Figueira RF 1977. Estudo experimental sobre a ação terapêutica da droga RO 7 - 1051 na infecção por diferentes cepas do Trypanosoma cruzi. Rev Inst Med Trop São Paulo 19: 335-341.
4. Andrade SG, Andrade ZA, Figueira RM 1977. Estudo experimental sobre a resistência de uma cepa ao Bay 2502. Rev Inst Med Trop São Paula 19: 124-129.
5. Andrade SG, Costa Silva R, Santiago CM 1989. Treatment of chronic experimental Trypanosoma cruzi infections in mice with MK-436, a 2-substituted 5-nitroimidazole. Bull WHO 67: 509-514.
6. Andrade SG, Figueira RM, Carvalho ML, Gorini DF 1975. Reaction of the Trypanosoma cruzi strain to the experimental therapeutical response to Bay 2502 (results of long term treatment). Rev Inst Med Trop São Paulo 17: 380-399.
7. Andrade SG, Freitas LAR, Peyrol S, Pimentel AR, Sadigursky M 1991. Experimental chemotherapy of Trypanosoma cruzi infection persistence of parasite antigens and positive sorology in parasitologically cured mice. Bull WHO 69: 191-199.
8. Andrade SG, Pimentel AR, de Souza MM, Andrade ZA 2000. Interstitial dendritic cells of the heart harbor Trypanosoma cruzi antigens in experimentally infected dogs: importance for the pathogenesis of chagasic myocarditis. Am J Trop Med Hyg 63: 64-70.
9. Andrade ZA 1999. Immunopathology of Chagas disease. Mem Inst Oswaldo Cruz 94 (Suppl I): 71-80.
10. Anez N, Carrasco H, Parada H, Crisante G, Rojas A, Fuenmayor C, Gonzalez N, Percoco G, Borges R, Guevara P, Ramirez JL 1999. Myocardial parasite persistence in chronic chagasic patients. Am J Trop Med Hyg 60: 726-732.
11. Apt W, Aguilera X, Arribada A, Ferez C, Miranda C, Sanchez G, Zulantay I, Cortes P, Rodriguez J, Juri D 1998. Treatment of chronic Chagas disease with itraconazole and allopurinol. Am J Trop Med Hyg 59: 133-138.
12. Araújo MS, Martins-Filho OA, Pereira ME, Brener Z 2000. A combination of benznidazole and ketoconazole enhances efficacy of chemotherapy of experimental Chagas disease. J Antimicrob Chemother 45: 819-824.
13. 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.
14. Á vila H, Sigman DS, Cohen LM, Millikan RC, Simpson L 1991. Polymerase chain reaction amplification of Trypanosoma cruzi kinetoplast minicircle DNA isolated from whole blood lysates: diagnosis of chronic Chagas disease. Mol Biochem Parasitol 48: 211-222.
15. Bankova VS, De Castro SL, Marcucci MC 2000. Propolis: recent advances in research on chemistry and plant origin. Apidologie 31: 3-15.
16. Bastos JK, Albuquerque S, Silva ML 1999. Evaluation of the trypanocidal activity of lignans isolated from the leaves of Zanthoxylum naranjillo. Planta Med 65: 541-544.
17. Batista R, Chiari E, de Oliveira AB 1999. Trypanosomicidal kaurane diterpenes from Wedelia paludosa. Planta Med 65: 283-284.
18. Berger I, Passreiter CM, Caceres A, Kubelka W 2001. Antiprotozoal activity of Neurolaena lobata. Phytother Res 15: 327-330.
19. Bocca-Tourres LC 1969. La enfermedad de Chagas en período agudo y su tratamiento con el Bay 2502. Bol Chil Parasitol 24: 24-27.
20. Bock M, Gonert R, Haberkorn A 1969. Studies with Bay 2502 on animals. Bol Chil Parasitol 24: 13-19.
21. Bodley AL, Shapiro TA 1995. Molecular and cytotoxic effects of carnptothecin, a topoisomerase I inhibitor, on trypanosomes and Leishmania. Proc Natl Acad Sci USA 92: 3726-3730.
22. Boechat N, Carvalho AS, Feraandez-Ferreira E, Soares RO, Souza AS, Gibaldi D, Bozza M, Pinto AC 2001. Novel nitroimidazoles with trypanocidal and cell growth inhibition activities. Cytobios 105: 83-90.
23. Bogitsh BJ, Middleton OL, Ribeiro-Rodrigues R 1999. Effects of the antitubulin drug trifluralin on the proliferation and metacyclogenesis of Trypanosoma cruzi epimastigotes. Parasitol Res 85: 475-480.
24. Bonay P, Duran-Chica I, Fresno M, Alarcon B, Alcina A 1998. Antiparasitic effects of the intra-Golgi transport inhibitor megalomicin. Antimicrob Agents Chemother 42: 2668-2673.
25. 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.
26. 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.
27. Brener Z 1961. Atividade terapêutica do 5-nitrofuraldeido-semicarbazona (nitrofurazona) em esquemas de duração prolongada na infecção experimental pelo Trypanosoma cruzi. Rev Inst Med Trop São Paulo 3: 43-49.
28. Brener Z 1968. Terapêutica experimental da doença de Chagas. In JR Cançado, Doença de Chagas. Belo Horizonte, Imprensa Oficial de Minas Gerais, Minas Gerais, p. 510-516.
29. Brener Z 1975. Chemotherapy of Trypanosoma cruzi infection Adv Pharmacol Chemother 13: 1-44.
30. Brener Z 1979. Present status of chemotherapy and chemoprofilaxis of human trypanosomiasis in the Western hemisphere. PharmacTherap 7: 71-90.
31. Brener Z 1984. Recent advances in chemotherapy of Chagas disease. Mem Inst Oswaldo Cruz 79 (Suppl): 149-155.
32. a ed., Guanabara Koogan, Rio de Janeiro, p. 379-388.
33. a ed., Guanabara Koogan, Rio de Janeiro, 431 pp.
34. Brener Z, Tafuri WL, Maria TA 1969. An electron microscope study on Trypanosoma cruzi intracellular forms in mice treated with active nitrofuran compound. Rev Inst Med Trop São Paulo 11: 245-249.
35. Brener Z, Cançado JR, Galvão LM, Da Luz ZM, Filardi LS, Pereira ME, Santos LM, Cançado CB 1993. An experimental and clinical assay with ketoconazole in the treatment of Chagas disease. Mem Inst Oswaldo Cruz 88: 149-153.
36. Brengio SD, Belmonte SA, Guerreiro E, Giordano OS, Pietrobon EO, Sosa MA 2000. The sesquiterpene lactone dehydroleucodine (DhL) affects the growth of cultured epimastigotes of Trypanosoma cruzi. J Parasitol 86: 407-412.
37. Bressi JC, Verlinde CL, Aronov AM, Shaw ML, Shin SS, Nguyen LN, Suresh S, Buckner FS, Van Voorhis WC, Kuntz ID, Hol WG, Gelb MH 2001. Adenosine analogues as selective inhibitors of glyceraldehyde-3-phosphate dehydrogenase of trypanosomatidae via structure-based drug design. J Med Chem 44: 2080-2093.
38. Britto C, Cardoso MA, Vanni CMM, Haslocher-Moreno A, Xavier SS, Wincker P 1995. Polymerase chain reaction detection of Trypanosoma cruzi in human blood samples as a tool for diagnosis and treatment evaluation. Parasitology 110: 241-247.
39. Britto C, Silveira C, Cardoso MA, Marques P, Luquetti A, Macedo V, Fernandes O 2001. Parasite persistence in treated chagasic patients revealed by xenodiagnosis and polymerase chain reaction. Mem Inst Oswaldo Cruz 96: 823-826.
40. Bronia DH, Pereira BM, Lujan HD, Fretes RE, Fernandez A, Paglini PA 1999. Ganglioside treatment of acute Trypanosoma cruzi infection in mice promotes long-term survival and parasitological cure. Ann Trop Med Parasitol 93: 341-350.
41. Bsiri N, Johnson C, Kayirere M, Galy AM, Galy JP, Barbe J, Osuna A, Mesa-Valle MC, Castilla Calvente JJ, Rodriguez-Cabezas MN 1996. Trypanocidal structure-activity relationship in 9-thioalkylacridines. Ann Pharm Fr 54: 27-33.
42. Buckner FS, Griffin JH, Wilson AJ, Van Voorhis WC 2001. Potent anti-Trypanosoma cruzi activities of oxidosqualene cyclase inhibitors. Antimicrob Agents Chemother 45: 1210-1215.
43. Buckner FS, Wilson AJ, White TC, Van Voorhis WC 1998. Induction of resistance to azole drugs in Trypanosoma cruzi. Antimicrob Agents Chemother 42: 3245-3250.
44. Caceres A, Lopez B, Gonzalez S, Berger I, Tada I, Maki J 1998. Plants used in Guatemala for the treatment of protozoal infections. I. Screening of activity to bacteria, fungi and American trypanosomes of 13 native plants. J Ethnopharmacol 62: 195-202.
45. Camargo ME 1966. Fluorescent antibody test for serodiagnosis of American Trypanosomiasis. Technical modification employing preserved culture forms of Trypanosoma cruzi in a slide test. Rev Inst Med Trop Sãv Paulo 8: 227-234.
46. Cançado JR 1963. Aspectos clínicos na padronização dos métodos de avaliação terapêutica na doença de Chagas. Rev Goiana Med 9 (Supl.): 212-232.
47. Cançado JR 1968. Tratamento da doença de Chagas. In JR Cançado, Doença de Chagas, Imprensa Oficial de Minas Gerais, Minas Gerais, p. 517-540.
48. Cançado JR 1981. Standartization of protocols for chemotherapy of Chagas disease (Working paper for discussion) Workshop on Standartizacion of Protocols for the Chemotherapy of Chagas Disease UNDP/World Bank/TDR. PAHO, Washington, November, 22-26.
49. Cançado JR 1985. Tratamento específico. In JR Cançado, M Chuster (eds), Cardiopatia Chagásica. Imprensa Oficial de Minas Gerais, Minas Gerais, p. 327-355.
50. Cançado JR 1997. Terapêutica específica. In JCP Dias, JR Coura, Clínica e Terapêutica da Doença de Chagas. Uma Abordagem Prática para o Clínico Geral. Fiocruz, Rio de Janeiro, p. 323-351.
51. Cançado JR 1999. Criteria of Chagas disease cure. Mem Inst Oswaldo Cruz 94 (Suppl I): 331-335.
52. a ed., Guanabara Koogan, Rio de Janeiro, p. 389-405.
53. Cançado JR, Brener Z 1979. Terapeutica. In Z Brener, Z Andrade (eds), Trypanosoma cruzi e Doença de Chagas, Guanabara Koogan, Rio de Janeiro, p. 362-424
54. Cançado JR, Marra UD, Brener Z 1964. Ensaio terapêutico clínico com a 5-nitro-2-furaldeido-semicarbazona (Nitrofurazona) na forma crônica da doença de Chagas. Rev Inst Med Trop São Paulo 6: 12-16.
55. Cançado JR, Marra UD, Lopes M, Mourão O, Faria CAF, Álvares JM, Salgado AA 1969. Toxicidade y valor terapêutico del Bay 2502 en la enfermedad de Chagas in tres esquemas posológicos. Bol Chil Parasitol 24: 28-32.
56. Cançado JR, Duval Marra U, Mourão OG, Álvares JM, Oliveira J, Salgado A 1973. Bases para avaliação do tratamento específico da doença de Chagas humana segundo a parasitemia. Rev Soc Bras Med Trop 7: 155-166.
57. Cançado JR, Salgado AA, Marra UD, Alvares JM, Machado JR 1975. Clinical therapeutic trial in chronic Chagas disease using nifurtimox in 3 schedules of long duration. Rev Inst Med Trop São Paulo 17: 111-127.
58. Cançado JR, Salgado AA, Batista SM, Chiari C 1976. Segundo ensaio terapêutico com nifurtimox na doença de Chagas. Rev Goiana Med 22: 203-233.
59. Castilla JJ, Mesa-Valle CM, Sanchez-Moreno M, Arncdo T, Rosales MJ, Mascaro C, Craciunescu D, Osuna A 1996. In vitro activity and biochemical effectiveness of new organometallic complexes of osmium(III) against Leishmania donovani and Trypanosoma cruzi. Arznein Forsch 46: 990-996.
60. Cazzulo JJ, Stoka V, Turk V 2001. The major cysteine proteinase of Trypanosoma cruzi: a valid target for chemotherapy of Chagas disease. Curr Pharm Des 7: 1143-1156.
61. Cerecetto H, Di Maio R, Gonzalez M, Risso M, Saenz P, Seoane G, Denicola A, Peluffo G, Quijano C, Olea-Azar C 1999. 1,2,5-Oxadiazole N-oxide derivatives and related compounds as potential antitrypanosomal drugs: structure-activity relationships. J Med Chem 42: 1941-1950.
62. Cerecetto H, Di Maio R, Gonzalez M, Risso M, Sagrera G, Seoane G, Denicola A, Peluffo G, Quijano C, Stoppani AO, Paulino M, Olea-Azar C, Basombrio MA 2000. Synthesis and antitrypanosomal evaluation of E-isomers of 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives. Structure-activity relationships. Eur J Med Chem 35: 343-350.
63. Cerisola JA, Rabionvich A, Alvarez M, Corleto CA, Prumeda J 1972. Enfermedad de Chagas y la transfusión de sangue. Bol Of Sanit Panam 73: 203-221.
64. Cerisola JA, Silva NN, Prata A, Schenone H, Rohwedder R 1977. Evaluación mediante xenodiagnostico de la efectividad del nifurtimox en la infección chagásica crónica humana. Bol Chil Parasitol 32: 51-62.
65. Chagas C, Chagas E 1935. Manual de Doenças Tropicaes e Infectuosas, Vol. I, Editora Freitas Bastos, Rio de Janeiro, 189 pp.
66. 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.
67. Chataing B, Concepcion JL, Lobaton R, Usubillaga A 1998. Inhibition of Trypanosoma cruzi growth in vitro by Solanum alkaloids: a comparison with ketoconazole. Planta Med 64: 31-36.
68. Chiari E, Brener Z 1966. Contribuição ao diagnóstico parasitológico da doença de Chagas na fase crônica. Rev Inst Med Trop São Paulo 8: 134-138.
69. Chiari E, Dias JCP, Lana M, Chiari CA 1989. Hemocultures for the parasitological diagnosis of human chronic Chagas disease. Rev Soc Bras Med Trop 22: 19-23.
70. Chiari E, Oliveira AB, Prado MA, Alves RJ, Galvão LM, Araújo FG 1996. Potential use of WR6026 as prophylaxis against transfusion-transmitted American trypanosomiasis. Antimicrob Agents Chemother 40: 613-615.
71. Chowdhury SF, Di Lucrezia R, Guerrero RH, Brun R, Goodman J, Ruiz-Perez LM, Pacanowska DG, Gilbert IH 2001. Novel inhibitors of leishmanial dihydrofolatereductase. Bioorg Med Chem Lett 11: 977-980.
72. Chung MC, Gonçalves MF, Colli W, Ferreira EI, Miranda MT 1997. Synthesis and in vitro evaluation of potential antichagasic dipeptide prodrugs of primaquine. J Pharm Sci 86: 1127-1131.
73. Cinque GM, Szajnman SH, Zhong L, Docampo R, Schvartzapel AJ, Rodriguez JB, Gros EG 1998. Structure-activity relationship of new growth inhibitors of Trypanosoma cruzi. J Med Chem 41: 1540-1554.
74. Clark AM 1996. Natural products as a resource for new drugs. Pharmaceutical Res 13:1133-1141.
75. Costa Silva R, Santiago CM, Pontes AL, Andrade SG 1990. Isoenzymatic pattern of Trypanosoma cruzi Y strain after specific chemotherapy. Mem Inst Oswalde Cruz 84: 81-86.
76. Coura JR 1996. Perspectivas actuales del trataamiento específico de la enfermedad de Chagas. Bol Chu Parasitol 51:69-75.
77. Coura JR, Silva JR 1961. Aspectos atuais do tratamento da doença de Chagas. Rev Bras Med 51: 283-290.
78. Coura JR, Ferreira LF, Saad EA, Mortel RE, Silva JR 1961. Tentativa terapêutica com a nitrofurazona (Furacin) na forma crônica da doença de Chagas. O Hospital 60: 425-429.
79. Coura JR, Ferreira LF, Silva JR 1962. Experiências com nitrofurazona na fase crônica da doença de Chagas. O Hospital 62: 957-964.
80. Coura JR, Brindeiro PJ, Ferreira I 1978. Benznidazole in the treatment of Chagas disease. Current Chemotherapy. Proc 10 th Int Cong Chemotherapy 1: 161-162.
81. Coura JR, de Abreu LL, Willcox HP, Petana W 1991. Evaluation of the xenodiagnosis of chronic Chagas patients infected ten years or over in an area where transmission has been interrupted-Iguatama and Pains, West Minas Gerais State, Brazil. Mem Inst Oswaldo Cruz 86: 395-398.
82. Coura JR, de Abreu LL, Willcox HP, Petana W 1997. Comparative controlled study on the use of benznidazole, nifurtimox and placebo, in the chronic form of Chagas disease, in a field area with interrupted transmission. I. Preliminary evaluation. Rev Soc Bras Med Trop 30: 139-144.
83. Croft SL 1994. A rationale for antiparasite drug discovery. Parasitol Today 10: 385-386.
84. Croft SL, Snowdon D, Yardley V 1996. The activities of four anticancer alkyllysophospholipids against Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. J Antimicrob Chemother 38: 1041-1047.
85. Dantas AP 2000. Efeito de agentes anti-microtúbulos e de derivados de naftoquinonas sobre Trypanosoma cruzi, MSc Thesis, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, xiv + 204 pp.
86. Dantas AP, Ortigão M, Traub-Czebo Y, Polaquevitch PFC, Barbosa HS, De Castro SL 1998. Studies on the effect of dinitroaniline herbicides in Trypanosoma cruzi. Mem Inst Oswaldo Cruz 93 (suppl II): 311
87. De Castro SL 1993. The challenge of Chagas disease chemotherapy: an update of drugs assayed against Trypanosoma cruzi. Acta Trop 53: 83-98.
88. De Castro 2001. Propolis: Biological and pharmacological activities. Therapeutic uses of this bee-product. Ann Rev Biol Sci, in press.
89. De Castro SL, Higashi KO 1995. Effect of different formulations of propolis on mice infected with Trypanosoma cruzi. J Ethnopharmacol 46: 55-59.
90. De Castro SL, Pinto MCFR, Pinto AV 1994. Screening of natural and synthetic drugs against Trypanosoma cruzi: establishing a structure/activity relationship. Microbios 78: 83-90.
91. De Castro SL, Dantas AP, Salomão K, Prytzyk E, Pereira AS, Aquino Neto FR, Bankova VS 2001. Trypanocidal activity and chemical composition of Bulgarian samples of propolis. Proc. 4th COST-B9 Cong Antiprotozoal Chemother, Lisbon, Portugal.
92. De Conti R, Rita RM, de Souza EM, Melo PS, Haun M, De Castro SL, Durán N 1996. in vitro trypanocidal activities of a novel series of N, N-dimethyl-2-propen-1-amine derivative. Microbios 85: 83-87.
93. De Moura KCG, Emery FS, Neves-Pinto C, Pinto MCFR, Dantas AP, Salomão K, De Castro SL, Pinto AV 2001. Synthesis and trypanocidal activity of naphthoquinones isolated from Tabebuia and heterocyclic derivatives: a review from an interdisciplinary study. J Braz Chem Soc 12: 325-338.
94. Deharo E, Loyevsky M, John C, Balanza E, Ruiz G, Munoz V, Gordeuk VR 2000. Aminothiol multidentate chelators against Chagas disease. Exp Parasitol 94: 198-200.
95. Di Maio R, Cerecetto H, Seoane G, Ochoa C, Aran VJ, Perez E, Gomez Barrio A, Muelas S 1999. Synthesis and antichagasic properties of new 1,2,6-thiadiazin-3, 5-dione 1,1-dioxides and related compounds. Arznein Forsch 49: 759-763.
96. a ed., Guanabara Koogan, Rio de Janeiro, p. 48-74
97. Diaz de Toranzo EG, Castro JA, Franke de Cazzulo BM, Cazzulo JJ 1988. Interaction of benznidazole reactive metabolites with nuclear and kinetoplastic DNA, proteins and lipids from Trypanosoma cruzi. Experientia. 44: 880-881.
98. DoCampo R 2001. Recent developments in the chemotherapy of Chagas disease. Curr Pharm Design 7: 1157-1164.
99. DoCampo R, Moreno SNJ 1986. Free radical metabolism of antiparasitic agents. Fed Proceed 45: 2471-2476.
100. DoCampo R, Moreno SNJ 2001. Bisphosphonates as chemotherapeutic agents against trypanosomatids and Apicomplexan parasites. Current Drug Targets-Infectious Disorders 1: 51-61.
101. Dubin M, Fernandez Villamil SH, Stoppani AO 2001. Cytotoxicity of beta-lapachone, a naphthoquinone with possible therapeutic use. Medicina (B Aires) 61: 343-350.
102. Eakin AE, Guerra A, Focia PJ, Torres-Martinez J, Craig SP 1997. Hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi as a target for structure-based inhibitor design: crystallization and inhibition studies with purine analogs. Antimicrob Agents Chemother 41: 1686-1692.
103. Engel JC, Doyle PS, Palmer J, Bainton DF, McKerrow JH 1998a. Cysteine protease inhibitors after Golgi complex ultrastructure and function in Trypanosoma cruzi. J Cell Sci 111: 597-606.
104. Engel JC, Doyle PS, Hsieh I, McKerrow JH 1998b. Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med 188: 725-734.
105. Fairlamb AH 1999. Future prospects for the chemotherapy of Chagas disease. Medicina (B Aires) 59: 179-187.
106. Fairlamb AH, Cerami A 1992. Metabolism and functions of trypanothione in the kinetoplastida. Annu Rev Micorbiol 46: 695-729.
107. Fernandez-Gomez R, Zerrouk H, Sebti F, Loyens M, Benslimane A, Ouaissi MA 1994. Growth inhibition of Trypanosoma cruzi and Leishmania donovani infatum by different snake venoms: preliminary identification of proteins from Cerastes cerastes venom which interact with the parasites. Toxicon 32: 875-882.
108. Ferreira HO 1961. Forma aguda da doença de Chagas tratada pela nitrofurazona. Rev Inst Med Trap São Paulo 3: 287-289.
109. Ferreira HO 1962. Fase aguda da doença de Chagas. O Hospital 61: 307-311.
110. Ferreira HO 1976. Ensaio terapêutico-clínico com benznidazol na doença de Chagas. Rev Inst Med Trop São Paulo 18: 357-364.
111. Ferreira HO 1990. Tratamento da forma indeterminada da doença de Chagas com nifurtimox e benznidazol. Rev Soc Bras Med Trop 23: 209-211.
112. Ferreira HO, Prata A, Rassi A 1963. Administração prolongada de nitrofurazona no tratamento da doença de Chagas aguda. O Hospital 63: 131-139.
113. Ferreira MS, Nishioka SA, Rocha A, Silva AM 1997a. Doença de Chagas e imunossupressão. In JCP Dias, JR Coura (eds), Clínica e Terapêutica da Doença de Chagas. Fiocruz, Rio de Janeiro, p. 365-379.
114. Ferreira MS, Nishioka SD, Silvestre MT, Borges AS, Nunes-Araujo FR, Rocha A 1997b. Reactivation of Chagas disease in patients with AIDS: report of three new cases and review of the literature. Clin Infect Dis 25: 1397-1400.
115. Fichera L, Esteva M, Wimmer Z, Rodriguez JB, Gros EG 1995. Effects of juvenile hormone analogues (JHA) on the development of Trypanosoma cruzi. Z Naturforsch 50C: 578-580.
116. Fife Jr. EH, Mushel LH 1959. Fluorescent antibody technique for serodiagnosis of Trypanosoma cruzi infection. Proc Soc Exp Biol 101: 540-543.
117. Filardi LS, Brener Z 1982. Nitroinidazole-thiadiazole derivative with curative action in experimental Trypanosoma cruzi infection. Ann Trop Med Parasitol 76: 293-297.
118. Fournet A, Barrios AA, Munoz V 1994. Leishmanicidal and trypanocidal activities of Bolivian medicinal plants. J Ethnopharmacol 41: 19-37.
119. 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 Enzym Inhib 13: 1-9.
120. 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 biisbenziylisoquinoline alkaloids in acute and chronic Trypanosoma cruzi marine model. Int J Antimicrob Agents 13: 189-195.
121. Fragata Filho AA, Boianain E, Silva MAD, Correia EB, Borges Filho R, Martins C, Salene V, Batlouni M, Souza E 1995. Validade do tratamento etiológico da fase crônica da doença de Chagas com benznidazol. Arq Bras Cardiol 65 (Supl I): 71.
122. Fragoso SP, Goldenberg S 1992. Cloning and characterization of the gene encoding Trypanosoma cruzi DNA topoisomerase II. Mol Biochem Parasitol 55: 127-134.
123. Fragoso SP, Mattei D, Hines JC, Ray D, Goldenberg S 1998. Expression and cellular localization of Trypanosoma cruzi type II DNA topoisomerase. Mol Biochem Parasitol 94: 197-204.
124. Freitas JLP, Almeida JO 1949. Nova tecnica de fixação de complemento para a moléstia de Chagas (Reação quantitativa com antígeno geleificado de cultures de Trypanosoma cruzi). O Hospital 35: 787-800.
125. Freymann DM, Wenck MA, Engel JC, Feng J, Focia PJ, Eakin AE, Craig SP 2000. Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi. Chem Biol 7: 957-968.
126. Galhardo MCG, Martins, I, Hasslocher-Moreno A, Xavier SS, Coelho JMC, Vasconcellos ACV, Santos RR 1999. Reactivação da infecção por Trypanosoma cruzi em paciente com síndrome de imunodeficiência adquirida. Rev Soc Bras Med Trop 32: 291-294.
127. Galleano RH, Marr JJ, Sosa RR 1990. Therapeutic efficacy of allopurinol in patients with chronic Chagas disease. Am J Trop Med Hyg 43: 159-166.
128. Girault S, Davioud-Charvet E, Salmon L, Berecibar A, Debreu MA, Sergheracrt C 1998. Structure-activity relationships in 2-aminodiphenylsulfides against trypanothione reductase from Trypanosoma cruzi. Bioorg Med Chem Lett 8: 1175-1180.
129. Girault S, Grellier P, Berecibar A, Maes L, Mouray E, Lemiere P, Debreu MA, Davioud-Charvet E, Sergheraert C 2000. Antimalarial, antitrypanosomal, and antileishmanial activities and cytotoxicity of of bis(9-amino-6-chloro-2-methoxyacridines): influence of the linker. J Med Chem 43: 2646-2654.
130. Gonrales-Perdomo M, De Castro SL, Meirelles MN, Goldenberg S 1990. Trypanosoma cruzi proliferation and differentiation arc blocked by topoisomerase II inhibitors. Antimicrob Agents Chemother34: 1707-1714.
131. Gonzalez-Martin G, Figueroa C, Merino I, Osuna A 2000. Allopurinol encapsulated in polycyanoacrylate nanoparticles as potential lysosomatropic carrier: preparation and trypanocidal activity. Eur J Pharm Biopharm 49: 137-142
132. Gonzalez-Martin G, Merino I, Rodriguez-Cabezas MN, Torres M, Nunez R, Osuna A, 1998. Characterization and trypanocidal activity of nifurtimox-containing and empty nanoparticles of polyethylcyanoacrylates. J Pharm Pharmacol 50: 29-35.
133. Grellier P, Sinou V, Garreau-de Loubresse N, Bylen E, Boulard Y, Schrevel J 1999. Selective and reversible effects of Vinca alkaloids on Trypanosoma cruzi epimastigote forms: blockage of cytokinesis without inhibition of the organelle duplication. Cell Motil Cytoskeleton 42: 36-47.
134. Guerreiro C, Machado A 1913. Da reação de Bordet e Gengou na moléstia de Carlos Chagas como elemento de diagnóstico. Brasil Med 27: 225-226.
135. 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.
136. Henderson GB, Ulrich P, Fairlamb AH, Rosemberg I, Pereira M, Sela M, Cerami A 1988. "Subversive" substrates for the enzyme trypanothione disulphide reductase, alternative approach to chemoterapy of Chagas disease. Proc Natl Acad Sci USA 85: 5374-5378.
137. Higashi KO, De Castro SL 1994. Propolis extracts are effective against Trypanosoma cruzi and have an impact on its interaction with host cells. J Ethnopharmacol 43: 149-155.
138. Higuchi ML 1999. Human chagasic cardiopathy: participation of parasite antigens, subsets lymiphocytes, cytokines and microvascular abnormalities. Mem Inst Oswaldo Cruz 94 (Suppl I): 263-267.
139. Higuchi ML, Brito T, Reis M, Bellotti G, Pereira-Barreto AC, Pileggi F 1993. Correlation between Trypanosoma cruzi parasitism and myocardial inflammation in human chronic chagasic myocardits. Light microscopy and immunohistochemical findings. Cardiovasc Pathol 2: 101-106.
140. + T cell dependent. Am J Trop Med Hyg 56: 485-489.
141. Hoare CA, Wallace FG 1966. Developmental stages of trypanosomatid flagellates: a new terminology. Nature 244: 69-70.
142. Hoffmann BK 1972. Toxicological investigations on the tolerability of nifurtimox. Arzeneim Forsch 22: 1590-1603.
143. Ianni BM, Arteaga E, Mady C, Barretto ACP, Pileggi F 1993. Uso de benznidazol em chagásicos na forma indeterminada: Resultados a longo prazo. Arq Bras Cardioi 61 (Supl II): 130.
144. Jatene AD, Costa R, Jatene MB 1997. Tratamento cirúrgico da cardiopatia chagásica. In JCP Dias, JR Coura (eds), Clínica e Terapêutica da Doença de Chagas. Fiocruz, Rio de Janeiro, p. 255-265.
145. Jones EM, Colley DG, Tostes S, Lopes ER, Venencak-Jones C, Mc Curley TL 1993. Amplification of Trypanosoma cruzi DNA sequence from inflammatory lesions inhuman chagasic cardiomyopathy. Am J Trop Med Hyg 48: 348-357.
146. Junqueira ACV, Chiari E, Wincker P 1996. Comparison of the polymerasc chain reaction with two classical parasitological methods, for diagnosis of Chagas disease in endemic region of North-Eastern Brazil. Trans R Soc Trop Med Hyg 90: 129-132.
147. Kelser RA 1936. A complement fixation test for Chagas disease employing an artificial culture antigen. Am J Trop Med Hyg 16: 405-415.
148. Kerschmann RL, Wolfson JS, McHugh GL, Dickersin GR, Hooper DC, Swartz MN 1989. Novobiocin-induced ultrastructural changes and antagonism of DNA synthesis in Trypanosoma cruzi amastigotes growing in cell-free medium. J Protozool 36: 14-20.
149. Kinnamon KE, Poon BT, Hanson WL, Waits VB 1996. Primaquine analogues that are potent anti-Trypanosoma cruzi agents in a mouse model. Ann Trop Med Parasitol 90: 467-474.
150. Kinnamon KE, Poon BT, Hanson WL, Waits VB 1997. Evidence that certain 8-aminoqumolines are potentially effective drugs against Chagas disease. Ann Trop Med Parasitol 91: 147-52.
151. Krauth-Siegel RL, Enders B, Henderson GB, Fairlamb AH, Schirmer RH 1987. Trypanothione reductase from Trypanosoma cruzi. Purification and characterization of the crystalline enzyme. Eur J Biochem 164: 123-128.
152. Krettli AU, Brener Z 1982. Resistance against Trypanosoma cruzi associate to anti-living trypomastigote antibodies. J Immunol 128: 2009-2012.
153. Kretth AU, Cançado JR, Brener Z 1984. Criterion of cure of human Chagas disease after especific treatment recent advances. Mem Inst Oswaldo Cruz 79 (Suppl): 157-164.
154. Lalmanach G, Mayer R, Serveau C, Scharfstein J, Gauthier F 1996. Biotin-labelled peptidyl diazomethane inhibitors derived from the substrate-like sequence of cystatin: targeting of the active site of cruzipain, the major cysteine proteinase of Trypanosoma cruzi. Biochem J 318: 395-399.
155. Lane JE, Ribeiro-Rodrigues R, Suarez CC, Bogitsh BJ, Jones MM, Singh PK, Carter CE 1996. In vitro trypanocidal activity of tetraethylthiuram disulfide and sodium diethylamine-N-carbodithioate on Trypanosoma cruzi. Am J Trop Med Hyg 55: 263-266.
156. Lane JE, Bogitsh BJ, Ribeiro-Rodrigues R, Kral MV, Jones MM, Carter CE 1998. Ultrastructural effects of the chelating agent 1,10-phenanthroline on Trypanosoma cruzi epimastigotes in vitro. Parasitol Res 84. 399-402.
157. Lauria-Pires L, Castro CN, Emanuel A, Prata A 1988. Ineficácia do allopurinol em pacientes na fase aguda da doençade Chagas. Rev Soc Med Trop 21: 79
158. Lazzari JO, Freihj H 1998. Tratamiento de la enfermedad de Chagas crónica en Argentina. Rev Patol Trop 27 (Supl): 11-16.
159. 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.
160. Lira R, Contreras LM, Rita RM, Urbina JA 2001. Mechanism of action of anti-pioliferative lysophospholipid analogues against the protozoan parasite Trypanosoma cruzi: potentiation of in vitro activity by the sterol biosynthesis inhibitor ketoconazole. J Antimicrob Chemother 47: 537-546.
161. Lopes JN, Cruz FS, DoCampo R, Vasconcellos ME, Sampaio MCR, Pinto AV, Gilbert B 1978. In vitro and in vivo evaluation of the toxicity of 1,4-naphthoquinone and 1,2-naphthoquinone derivatives against Trypanosoma cruzi. Ann Trop Med Parasitol 72: 523-531.
162. Lujan HD, Paglini P, Fretes R, Fernandez A, Fidelio GD, Bronia DH 1993.
163. Luque F, Femandez-Ramos C, Entrala E, Resales MJ, Navarro JA, Romero MA, Salas JM, Sanchez-Moreno M 2000. In vitro evaluation of newly synthesized [1,2,4]triazolo[1, 5a]pyrimidine derivatives against Trypanosoma cruzi, Leishmania donovani and Phylomonas staheli. Comp Biochem Physiol C Taxicol Pharmacol 126: 39-44.
164. Luquetti 1997. Etiological treatment for Chagas disease. The National Health Foundation of Brazil. Parasitol Today 13: 127-128.
165. Luz ZMP, Coutinho MG, Cançado JR, Krettli AU 1994. Hemocultura: técnica sensível na detecção do Trypanosoma cruzi em pacientes chagásicos crônicos. Rev Soc Bras Med Trop 27: 143-148.
166. Macêdo VO 1997. Forma indeterminada da doença de Chagas. In JCP Dias, JR Coura (eds), Clínica e Terapêutica da Doença de Chagas. Uma Abordagem Prática para o Clínico Geral. Fiocruz, Rio de Janeiro, p. 383-409.
167. Macêdo VO, Silveira CA 1987. Perspectivas da terapêutica específica na doença de Chagas. Experiências na forma indeterminada. Rev Soc Bras Med Trop 20 (Supl II): M24-M26.
168. Mafezoli J, Vieira PC, Fernandes JB, Da Silva MF, De Albuquerque S 2000. In vitro activity of Rutaceae species against the trypomastigote form of Trypanosoma cruzi. J Ethnopharmacol 73: 335-340.
169. Mahiou V, Roblot F, Fournet A, Hocquemiller R 2000. Bisbenzylisoquinoline alkaloids from Guatteria boliviana (Annonaceae). Phytochemistry 54: 709-716.
170. Marcucci MC, Ferreres F, García-Viguera C, Bankova VS, De Castro SL, Dantas AP, Valente PHM, Paulino N 2001. Phenolic compounds from Brazilian propolis with pharmacological activities. J Ethnopharmacol 74: 105-112.
171. Marr JJ 1991. Punne analogs as chemotherapeutic agents in leishmaniasis and American trypanosomiasis. J Lab Clin Med 118: 111-119.
172. Martin MB, Grimley JS, Lewis JC, Heath HT, 3rd, Bailey BN, Kendrick H, Yardley V, Caldera A, Lira R, Urbina JA, Moreno SN, Docampo R, Croft SL, Oldfield E 2001. Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Letshmania donovani, Toxoplasma gondii, and Plasmodium falciparum: A potential route to chemotherapy. J Med Chem 44: 909-916.
173. Maya JD, Morello A, Repetto Y, Tellez R, Rodriguez A, Zelada U, Puebla P, Caballero E, Medarde M, Nunez-Vergara LJ, Squella JA, Bonta M, Bollo S, San Feliciano A 2000. Effects of 3-chloro-phenyl-1,4-dihydropyridine derivatives on Trypanosoma cruzi epimastigotes. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 125: 103-109.
174. Mayer M, Rocha Lima H 1912. Zur Entwicklung von Schizotrypanum cruzi in Saengatieren. Arch Schisffs u Tropen Hyg 16: 90-94.
175. Mayer M, Rocha Lima H 1914. Zum Verhalten von Schizotrypanum cruzi in Warmbluetern und Arthropoden. Arch Schiffs u Tropen-Hyg 5: 101-136.
176. Mazza S, Cossio R, Zucardi E 1937. Primer caso agudo de enfermedad de Chagas, comprovado em Tucuman y su tratamiento com Bayer 7602. Mis Estudios Patolog Reg Argentina Publ 70 (Univ Buenos Aires) (MEPKA) 32: 3-18.
177. Mazza S, Basso G, Basso R 1942. Ensayos terapéuticos del produto 9736 (As) Bayer y de su acción comparada en el 7602 (Ac) Bayer en la enfermedad de Chagas. Mis Estudios Patolog Reg Argentina Publ 70(Univ Buenos Aires) (MEPRA) 61: 1-76.
178. McKerrow JH 1999. Development of cysteine protease inhibitors as chemotherapy for parasitic diseases: Insights on safety, target validation, and mechanism of action, Int J Parasitol 29. 833-837.
179. Medrano NM, Luz MRMP, Cabello P, Tapia GT, Van Leuven F, Araújo-Jorge TC 1996. Acute Chagas disease: Plasma levels of alpha-2-macroglobulin and C-reactive protein in children der 13 years in a high endemic area of Bolivia. J Trop Pediatr 42: 68-74.
180. Molina J, Martins-Filho O, Brener Z, Romanha AJ, Loebenberg D, Urbina JA 2000. Activities of the triazole derivative SCH 56592 (posaconazole) against drug-resistant strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi in immunocompetent and immunosuppressed murine hosts. Antimicrob Agents Chemother 44: 150-155.
181. Molina J, Urbina J, Gref R, Brener Z, Rodrigues Junior JM 2001. Cure of experimental Chagas disease by the bis-triazole DO870 incorporated into "stealth" polyethyleneglycol-polylactide nanospheres. J Antimicrob Chemother 47: 101-104.
182. Montalvetti A, Bailey BN, Martin MB, Severin GW, Oldfield E, DoCampo R 2001. Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase. J Biol Chem 276: 33930-33937.
183. Morello A, Lipchenca I, Cassels BK, Speisky H, Aldunate J, Repetto Y 1994. Trypanocidal effect of boldine and related alkaloids upon several strains of Trypanosoma cruzi. Comp Biochem Physiol Pharmacol Toxicol Endocrinol 107: 367-371.
184. Morello A, Pavani M, Garbarino JA, Chamy MC, Frey C, Mancilla J, Guerrero A, Repetto Y, Ferreira J 1995. Effects and mode of action of 1,4-naphthoquinones isolated from Calceolaria sessilis on tumoral cells and Trypanosoma parasites. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 112: 119-128.
185. Moser DR, Kirchoff LV, Donelson JE 1989. Detection of Trypanosoma cruzi by DNA amplification using the polymerase chain reaction. J Clin Microbiol 27: 1477-1482.
186. Muelas S, Di Maio R, Cerecctto H, Seoane G, Ochoa C, Escario JA, Gomez-Barrio A 2001. New thiadiazine derivatives with activity against Trypanosoma cruzi amastigotes. Folia Parasitol (Praha) 48: 105-108.
187. Muelas-Serrano S, Nogal JJ, Martinez-Diaz RA, Escario JA, Martinez-Fernandez AR, Gomez-Barrio A 2000. In vitro screening of American plant extracts on Trypanosoma cruzi and Trichomonas vaginalis. J Ethnopharmacol 71: 101-107.
188. Nakajima-Shimada J, Hirota Y, Aoki T 1996. Inhibition of Trypanosoma cruzi growth in mammalian cells by purine and pyrimidine analogs. Antimicrob Agents Chemother. 40: 2455-2458.
189. Neal RA, Miles RA 1970. Indirect hemaglutination test for Chagas disease, with a simple method for survey work. Rev Inst Med Trop São Paulo 12: 325-332.
190. Neira I, Poblete L, Porcille P, Silva P, Araya J, Borquez J, Morales G, Loyola LA, Sagua H 1998. Activity of Dipernoids isolated from Azorella compacta (Llareta) on Trypanosoma cruzi amastigotes. Bol Chil Parasitol 53: 9-13.
191. Neves-Pinto C, Dantas AP, De Moura KCG, Emery FS, Polequcvitch PF, Pinto MCFR, De Castro SL, Pinto AV 2000. Chemical reactivity studies with naphthoquinones from Tabebuia with anti-trypanosomal efficacy. Arzneim Forsch 50: 1120-1128.
192. Nunez-Vergara LJ, Squella JA, Bollo-Dragnic S, Morello A, Repetto Y, Aldunate J, Letelier ME 1997. Nitro aryl 1,4-dihydropyridinc derivatives: effects on Trypanosoma cruzi. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 118. 105-111.
193. Nussenzweig V, Sonntag R, Biancalana A, Freitas JLP, Amato Neto V, Kloetzel J 1953. Ação da violeta de genciana sobre o T. cruzi in vitro: sua importância na esterilização do sangue destinado à transfusāo. Rev Paul Med 42: 57-58.
194. Ochoa C, Perez E, Perez R, Suarez M, Ochoa E, Rodriguez H, Gomez Barrio A, Muelas S, Nogal JJ, Martinez RA 1999. Synthesis and antiprotozoan properties of new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives. Arznein Forsch 49: 764-769.
195. Oliveira DA, Fernandes AM, De Conti R, Rodriguez JA, Haun M, Souza-Brito AR, De Castro SL, Durán N 1999. Evaluaon of in vitro toxicity of N,N-dimethyl-2-propen-1-amines isomers. Pharmazie 54: 847-850.
196. Olmo E, Armas MG, Lopez-Perez JL, Ruiz G, Vargas F, Gimenez A, Deharo E, Feliciano AS 2001. Anti-Trypanoxoma activity of some natural stilbenoids and synthetic related heterocyclic compounds. Bioorg Med Chem Lett II: 755-757.
197. OPAS/OMS 1998. Tratamiento Etiológico de la Enfermedad de Chagas. Conclusiones de una consulta técnica. OPC/HCP/ HCT/140/99, 32 pp. (published in Rev Patol Trop 28: 247-279, 1999)
198. OPAS/OMS 1998. Tratamiento Etiológico de la Enfermedad de Chagas. Conclusiones de una consulta técnica. OPC/HCP/ HCT/140/99, 32 pp. (published in Rev Patol Trop 28: 247-279, 1999)
199. Packchanian A 1952. Chemotherapy of experimental Chagas disease with nitrofuran compounds. J Parasitol 38: 30-40.
200. Packchanian A 1957. Chemotherapy of experimental Chagas disease with nitrofuran compounds. Antibiotics & Chemotherapy 7: 13-23.
201. Paglini-Oliva P, Fernandez AR, Fretes R, Peslman A 1998. Structural, ultrastructural studies and evolution of Trypanosoma cruzi-infected mice treated with thioridazine. Exp Mol Pathol 65. 78-86.
202. Pereira DG, De Castro SL, Durán N 1998. Activity of N,N-dimethyl-1-2-propen-I-amine derivatives in mice experimentally infected with Trypanosoma cruzi. Acta Trop 69: 205-211.
203. Pifano FC 1941. La enfermedad de Chagas en el Estado Jaracuy, Venezuela. Caracas Medien 8: 1103-1166.
204. Pineda JP, Luquetti A, Castro C 1998. Comparison between classical and artificial xenodiagnosis in chronic Chagas disease. Rev Soc Bras Med Trop 31: 473-480.
205. Pinto AV, Neves Pinto C, Pinto MCFR, Santa-Rita RM, Pezzella C, De Castro SL 1997. Trypanocidal activity of synthetic heterocyclic derivatives from active quinones from Tabebuia sp. Arzneim-Forsch 4. 74-79.
206. Polak A, Richle R 1978. Mode of action of 2-nitroimidazole derivative benznidazole. Ann Trop Med Parasitol 72: 228-232.
207. Prata A 1963. Estado atual da terapeutica da doença de Chagas. Revisão dos medicamentos até hoje utilizados. Rev Gotana Medicina 9 (Supl.): 109-124.
208. Prata A, Macedo V, Santos I, Cerisola JA, Silva N 1975. Tratamento da doença de Chagas pelo nifurtimox (Bayer 2505). Rev Soc Brasil Med Trop 6: 297-308.
209. Rassi A, Ferreira HO 1971. Tentativas de tratamento específico da fase aguda da doença de Chagas com nitrofuranos em esquemas de duração prolongada. Rev Soc Bras Med Trop 5: 235- 262.
210. Rassi A, Luquetti AO 1992. Therapy of Chagas disease. In S Wendel, Z Brener, E Camargo, A Rassi (eds), Chagas Disease (American Trypanosomiasis): its Impact on Transfusion and Clinical Medicine. ISBT, São Paulo, p. 237-247.
211. Rassi A, Amato Neto V, De Siqueira AF, Ferriolli Filho F, Amato VS, Rassi Jr A 1999. Protective effect of benznidazole against parasite reactivation in patients chronically infected with Trypanosoma cruzi and treated with corticoids for associated diseases. Rev Soc Bras Med Trop 32: 475-482.
212. Reche P, Arrebola R, Santi DV, Gonzalez-Pacanowska D, Ruiz-Perez LM 1996. Expression and characterization of the Trypanosoma cruzi dihydrofolate reductase domain. Mol Biochem Parasitol 76: 175-185.
213. Rezende JM 1959. Forma digestiva da moléstia de Chagas. Rev Goiana Med 5: 193-220.
214. Rezende JM, Lauar KM, Oliveira AR 1960. Aspectos clínicos e radiológicos da aperistalsis do esôfago. Rev Bras Gastroenterol 12: 247-261.
215. Richle R 1973. Chemotherapy of experimental acute Chagas disease in mice, beneficial effect of Ro-71051 on parasitemia and tissue parasitism. Le Progres Medical 101: 282.
216. Rivarola HW, Fernandez AR, Enders JE, Fretes R, Gea S, Suligoy M, Palma JA, Paglini-Oliva P 1999. Thioridazine treatment modifies the evolution of Trypanosoma cruzi infection in mice. Ann Trop Med Parasitol 93: 695-702.
217. Rivas P, Cassels BK, Morello A, Repetto Y 1999. Effects of eta;-carboline alkaloids on intact Trypanosoma cruzi epimasugotes. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 122: 27-31.
218. Rodrigues RR, Lane JE, Carter CE, Bogitsh BJ, Singh PK, Zimmerman LJ, Molenda JJ, Jones MM 1995. Chelating agent inhibition of Trypanosoma cruzi epimastigotes in vitro. J Inorg Biochem 60: 277-288.
219. Rodriguez JB 2001. Specific molecular targets to control tropical diseases. Curr Pharm Des 7: 1105-1116.
220. Rodriguez JB, Gros EG 1995. Recent developments in the control of Trypansoma cruzi, the causative agents of Chagas disease. Curr Med Chem 2: 723-742.
221. Rodriguez JB, DoCampo R, Gros EG 2000. Sulphur-containing derivatives structurally related to fenoxycarb are potent growth inhibitors against the intracellular form of Trypanosoma cruzi. Int J Antimicrob Agents 13: 215-218.
222. Roush WR, Hernandez AA, McKerrow JH, Selzer PM, Hansell E, Engel JC 2000. Design, synthesis and evaluation of D-homophenylalanylepoxysuccinate inhibitors of the trypanosomal cystein protease cruzain. Tetrahedron 56: 9747-9762.
223. Rovai LE, Aoki A, Gerez de Burgos NM, Blanco A 1990. Effect of gossypol on trypomastigotes and amastigotes of Trypanosoma cruzi. J Protozool 37: 280-286.
224. Rubio M, Donoso F 1969. Enfermedad de Chagas en niños y tratamiento con Bay 2502. Bol Chil Parasitol 24: 43-48.
225. Ryley JF, McGregor S, Wilson RG 1988. Activity of ICI 195,739 - a novel orally active bistriazole - in rodent models of fungal and protozoal infection. Ann N Y Acad Sci 310: 328.
226. Sahnon-Chemin L, Buisine E. Yardley V, Kohler S, Debreu MA, Landry V, Sergheraert C, Croft SL, Krauth-Siegel RL, Davioud-Charvel 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.
227. Santa-Rita RM, Barbosa HS, Meirelles MNL, De Castro SL 2000. Effect of alkyllysophospholipids on the proliferation and differentiation of Trypanosoma cruzi. Acta Trop 75:219-228.
228. Santos AF, Ferraz PA, de Abreu FC, Chiari E, Goulart MO, Sant'Ana AE 2001. Molluscicidal and trypanocidal activities of lapachol derivatives. Planta Med 67: 92-3.
229. Schenone H, Concha L, Aranda R, Rojas A, Alfaro E 1969. Experiência terapêutica con el Bayer 2502 en la infección chagasica cronica del adulto. Importancia del uso adequado del xenodiagnóstico. Bol Chil Parasitol 24: 66-69.
230. Schenone H, Concha L, Aranda R, Rojas A, Alfaro E, Knierin E, Rojo M 1975. Atividade quimioterápica de um derivado nitromidazolacetamida na infecção chagásica crônica. Biol Chil Parasitol 30: 91-93.
231. Schenone H, Concha L, Aranda R, Rojas A, Knierim F, Rojo M 1972. Treatment of chronic Chagas infection with Lampit. Bol Chil Parasitol 27: 11-14.
232. Schenone H, Rojas A, Alfaro E, Concha L, Aranda R 1981. Estudio longitudinal de la persistencia de la acción terapéutica del nifurtimox y del benznidazol en pacientes con infección chagásica crónica. Bol Chil Parasitol 36: 59-62.
233. Schofield CJ, Dias JCP 1999. The Southern Cone Initiative against Chagas disease. Adv Parasitol 42: 1-27.
234. Schmeda-Hirschmann G, Astudillo L, Bastida J, Codina C, Rojas de Arias A, Ferreira ME, Inchaustti A, Yaluff G 2001. Cryptofolione derivatives from Cryptocarya alba fruits. J Pharm Pharmacol 53: 563-567.
235. Schmunis GA 1994. American trypanosomiasis as a public health problem. In PAHO, Chagas Disease and the Nervous System. Scientific Publ no 547, p. 3-29.
236. a ed., Guanabara Koogan, Rio de Janeiro, p. 1-15.
237. Silva NN, Kuhn G, Santos JFC, Von Eye G, Chaer JAB 1974. Eficácia e tolerância do nitrofurfurilidene na fase crônica da moléstia de Chagas. Rev Soc Bras Med Trop 88: 325-334.
238. Silveira JF 1992. Trypanosoma cruzi recombinant antigens for serodiagnosis. In S Wendel, Z Brener, E Camargo, A Rassi (eds), Chagas Disease (American Trypanosomiasis): its Impact on Transfusion and Clinical Medicine. ISBT, São Paulo, p. 207-218.
239. Silveira JF, Umezawa ES, Luquetti AO 2001. Chagas disease: Recombinant Trypanosoma cruzi antigens for serological diagnosis. Trends in Parasitology 17: 286-291.
240. Singh PK, Jones MM, Lane JE, Nesset A, Zimmerman LJ, Ribeiro-Rodrigues R, Richter A, Stenger MR, Carter CE 1997. Synthesis and in vitro trypanocidal activity of some novel iron chelating agents. Arznein Forsch 47: 311-315.
241. Solari A, Saavedra H, Sepulveda C, Oddó D, Acuna G, Labarca J, Muñoz S, Cuny G, Brengues C, Veas F, Bryan RT 1993. Successful treatment of Trypanosoma cruzi encephalitis in a patient with hemophilia and AIDS. Clin Inf Dis 16: 255-259.
242. Sosa Estani S, Segura EL, Ruiz AM, Velazquez E, Porcel BM, Yampotis C 1998. Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas disease. Am J Trop Med Hyg 59: 526-529.
243. Souza DH, Garratt RC, Araújo AP, Guimarães BG, Jesus WD, Michels PA, Hannacrt V, Oliva G 1998. Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase: structure, catalytic mechanism and targeted inhibitor design. FEBS Lett 424: 131-135.
244. Stoka V, Nycander M, Lenarcic B, Labriola C, Cazzulo JJ, Bjork I, Turk V 1995. Inhibition of cruzipain, the major cysteine proteinase of the protozoan parasite, Trypanosoma cruzi, by proteinase inhibitors of the cystatin superfamily. FEBS Lett 370: 101-104.
245. Stoppani AOM 1999. The chemotherapy of Chagas disease. Medicina (B Aires) 59: 147-165
246. Storino R, Galleano R, Sosa R 1994. Tratamento antiparasitário específico. In R Storino, J Milei (eds), Enfermedad de Chagas, Mosby Doyma, Argentina, p. 557-568.
247. Sturm NR, Degrave W, Morel CM, Simpson L 1989. Sensitive detection by amplification of kinetoplast minicircle DNA sequences: use in diagnosis of Chagas disease. Mol Biochem Parasitol 33: 205-214
248. Sundar S, Goyal AK, More DK, Singh MK, Murray HW 1998. Treatment of antimony-unresponsive Indian visceral leishmaniasis with ultra-short courses of amphotericin-B-lipid complex. Ann Trop Med Parasitol 92: 755-764.
249. Sundar S, Makharia A, More DK, Agrawal G, Voss A, Fischer C, Bachmann P, Murray HW 2000. Short-course of oral miltefosine for treatment of visceral leishmaniasis. Clin Infect Dis 31: 1110-1113.
250. Szajnman SH, Yan W, Bailey BN, DoCampo R, Elhalem E, Rodriguez JB 2000. Design and synthesis of aryloxyethyl thiocyanate derivatives as potent inhibitors of Trypanosoma cruzi proliferation. J Med Chem 43: 1826-1840.
251. Tarleton RL 2001. Parasite persistence in the aetiology of Chagas disease. Int J Parasitol 31: 550-554.
252. Teixeira AR, Cordoba JC, Souto Maior IC, Solorzano E 1990. Chagas disease: lymphoma growth in rabbits treated with benznidazole. Am J Trop Med Hyg 43: 146-158.
253. Teixeira AR, Calixto MA, Teixeira ML 1994. Chagas disease: carcinogenic activity of the antitrypanosomal nitroarenes in mice. Mutat Res 305: 189-196.
254. Thomas SM, McPhee DG 1984. Crystal violet: a direct- acting frameshift mutagen whose mutagemcity is enhanced by mammalian metabolism. Mutanon Res 140: 165-167.
255. Tomazela DM, Pupo MT, Passador EA, da Silva MF, Vieira PC, Fernandes JB, Fo ER, Oliva G, Pirani JR 2000. Pyrano chalcones and a flavone from Neoraputia magnifica and their Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase-inhibitory activities. Phytochemistry 55: 643-651.
256. Tomimori-Yamashita J, Deps PD, Almeida DR, Enokihara MM, De Seixas MT, Freymuller E 1997. Cutaneous manifestation of Chagas disease after heart transplantation: successful treatment with allopurinol. Dr J Dermacol 37: 626-630.
257. Traub-Cseko YM, Ramalho-Ortigao JM, Dantas AP, De Castro SL, Barbosa HS, Downing KH 2001. Dinitroaniline herbicides against protozoan parasites: the case of Trypanosoma cruzi. Trends Parasitol 17: 136-141.
258. Trouiller P, Rey JL, Bouscharain P 2000. Pharmaceutical development concerning diseases predominating in tropical regions: The concept of indigent drugs. Ann Pharm Fr 58: 43-46.
259. Ullman B, Carter D 1997. Molecular and biochemical studies on the hypoxanthine-guanine phosphoribosyltransferases of the pathogenic haemoflagellates. Int J Parasitol 27: 203-213.
260. Umezawa ES, Nascimento MS, Kesper Jr, Coura JR, Borges-Pereira J, Junqueira ACV, Camargo ME 1996. Immunoblot assay using excreted-secreted antigens of Trypanosoma cruzi in serodiagnosis of congenital, acute and chronic Chagas disease. J Clin Microbiol 37: 1554-1560.
261. Umezawa ES, Nascimento MS, Stolf AMS 2001. Enzime-linked immunosorbent assay with Trypanosoma cruzi excreted-secreted antigens (TESA-ELISA) for serodiagnosis of acute and chronic Chagas' disease. Diag Microbiol Infect Disease 39: 169-176.
262. Urbina JA 1999. Chemotherapy of Chagas disease: the how and the why. J Mol Med 77: 332-338.
263. Urbina JA, Payares G, Molina J, Sanoja C, Liendo A, Lazardi K, Piras MM, Piras R, Perez N, Wincker P, Ryley JF 1996. Cure of short- and long-term experimental Chagas disease using D0870. Science 273: 969-971.
264. Urbina JA, Moreno B, Vierkotter S, Oidfield E, Payares G, Sanoja C, Bailey BN, Yan W, Scott DA, Moreno SN, DoCampo R 1999 Trypanosoma cruzi contains major pyrophosphate stores, and its growth in vitro and in vivo is blocked by pyrophosphate analogs. J Biol Chem 274: 33609-33615.
265. Urbina JA, Lira R, Visbal G, Bartroli J 2000. In vitro antiproliferative effects and mechanism of action of the new triazole derivative UR-9825 against the protozoan parasite Trypanosoma (Schizotrypanum) cruzi. Antimicrob Agents Chemother 44: 2498-2502.
266. Viotti R, Vigliano C, Armenti H, Segura E 1994. Treatment of chronic Chagas disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up. Am Heart J 127: 151-162.
267. Voller A, Draper C, Bidwell DE, Bartlett A 1975. A micro-plate enzyme-linked immunosorbent assay (ELISA) for Chagas disease. The Lancet 1: 426-429.
268. Waechter AI, Yaluff G, Inchausti A, Rojas de Arias A, Hocquemiller R, Cavé A, Fournet A 1998. Leishmanicidal and trypanocidal activities of acetogenins isolated from Annona glauca. Phytotherapy Res 12: 541-544.
269. Wang CC 1997. Validating targets for antiparasite chemotherapy. Parasitology 114 (Suppl): S31-44.
270. Wendel S, Dias JCP 1992. Transfusion transmitted Chagas disease. In S Wendel, Z Brener, E Camargo, A Rassi (eds), Chagas Disease (American trypanosomiasis): its Impact on Transfusion and Clinical Medicine. ISBT, São Paulo, p. 103-134.
271. WHO-World Health Organization 1984. Meeting on the development of trypanocidal compounds for the sterilization of blood UNDP/WB/TDR, Geneve.
272. WHO-World Health Organization 1997. Chagas disease. Thirteenth Programme Report UNDP/TDR, Geneve.
273. Wieder T, Reutter W, Orfanos CE, Geilen CC 1999. Mechanisms of action of phospholipid analogs as anticancer compounds. Prog Lipid Res 38: 249-259.
274. Winker P, Britto C, Borges Pereira, Cardoso MA, Coleman W, Morel CM 1994. Use of simplified polymerase chain reaction procedures to detect, Trypanosoma cruzi in blood samples from chronic chagasic patients in rural area. Am J Trop Med Hyg 51: 771-777.
275. Yardley V, Croft SL 1999. In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections. Am J Trop Med Hyg 61: 193-197.
276. Yong V, Schmitz V, Vannier-Santo MA, de Lima AP, Lalmanach G, Juliano L, Gauthier F, Scharfstein J 2000. Altered expression of cruzipain and a cathepsin B-like target in a Trypanosoma cruzi. cell line displaying resistance to synthetic inhibitors of cysteine-proteinases. Mol Biochem Parasitol 109: 47-59.
277. Zaidenberg A, Tournier H, Schinella G, Marin G, Buschiazzo H 1999. Effects of triflurahn on Trypanosoma cruzi in vitro and in vivo. Pharmacol Toxicol 84: 98-100.
278. Zuccotto F, Brun R, Gonzalez Pacanowska D, Ruiz Perez LM, Gilbert IH 1999. The structure-based design and synthesis of selective inhibitors of Trypanosoma cruzi dihydrofolate reductase. Bioorg Med Chem Lett 9: 1463-1468.
279. Zuccotto F, Martin AC, Laskowski RA, Thornton JM, Gilbert IH 1998. Dihydrofolate reductase: a potential drug target in trypanosomes and leishmania. J Comput Aided Mol Des 12: 241-257.