The chemotherapy of Chagas disease;Quimiotherapia de la enfermedad de Chagas

Medicina

Volumn 59, Issue SUPPL. 2, 1999, Pages 147-165

  Stoppani, Andres O M ^a  

^a UNIVERSIDAD DE BUENOS AIRES   (Argentina)

Author keywords

Lapachona; Allopurinol; Azols; Benznidazole; Chagas disease; Chemotherapy Nifurtimox; Cruzipaina; Fenotiazinas; Gossipol; o Naftoquinonas; Tripanotiona reductasa; Trypanosoma cruzi

Indexed keywords

1,2,3,4 TETRAHYDROCARBAZOLE DERIVATIVE; 5 AMINO 4 IMIDAZOLECARBOXAMIDE; ACRIDINE DERIVATIVE; ALKYLLYSOPHOSPHOLIPID; ALLOPURINOL; ALLOPURINOL RIBOSIDE; AMPHOTERICIN B; ANTITRYPANOSOMAL AGENT; BENZNIDAZOLE; BISBENZYLISOQUINOLINE DERIVATIVE; CRYSTAL VIOLET; CYSTEINE PROTEINASE INHIBITOR; DACTINOMYCIN; DITERPENE; ECONAZOLE; KETOCONAZOLE; MEVINOLIN; MICONAZOLE; NIFURTIMOX; OLIVACINE; PHENAZINE METHOSULFATE; PHENOTHIAZINE DERIVATIVE; PRIMAQUINE; PROADIFEN; PYRROLE DERIVATIVE; SESQUITERPENE DERIVATIVE; SESQUITERPENE LACTONE DERIVATIVE; TERBINAFINE; TRIPHENYLMETHANE DERIVATIVE; UNINDEXED DRUG;

CHAGAS DISEASE; CONFERENCE PAPER; DRUG SENSITIVITY; DRUG STRUCTURE; GENOTOXICITY; HUMAN; NONHUMAN; STRUCTURE ACTIVITY RELATION; ANIMAL; CHEMISTRY; DRUG EFFECT; MOUSE; RAT; REVIEW; TRYPANOSOMA CRUZI;

ANIMALS; CHAGAS DISEASE; HUMANS; MICE; RATS; TRYPANOCIDAL AGENTS; TRYPANOSOMA CRUZI;

EID: 0033251504     PISSN: 00257680     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Conference Paper

References (221)

1. Moncayo A: Progress towards the elimination of transmission of Chagas disease in Latin America. Wld Hlth Statist Quart 1997; 50: 195-8.
2. Cançado JR, Brener Z: Terapeutica. In: Trypanosoma cruzi e doença de Chagas, (eds), Guanabara Koogan S.A., Rio de Janeiro, 1979; pp. 362-424.
3. Storino RA, Gallerano R, Sosa R: Tratamiento antipara-sitario especifico. In: Enfermedad de Chagas, (eds.), Buenos Aires, Mosby-Doyma Argentina S. A., 1994; pp 557-68.
4. Fairlamb A: Biochemistry of trypanosomiasis and rational approaches to chemotherapy. Trends Biochem Sci 1982; 7: 249-53.
5. Stoppani AOM: Rational approaches to Chagas' disease chemotherapy. In; New strategies for orphan drugs, (ed.), Accademia Nazionale delle Scienze, detta dei XL, Roma, 1986; pp. 125-39.
6. Marr JJ, Docampo R: Chemotherapy for Chagas' diseases :a perspective of current therapy and considerations for future research. Rev Infect Dis 1986; 8: 884-903.
7. Docampo R, Moreno SNJ: Free radical metabolism of antiparasitic agents. Fed Proc 1986; 45: 2471-6.
8. Morello A, Aldunate J, Letelier ME, Repetto Y: Bases bioquímicas de la acción de drogas antichagásicas. Arch Biol Med Exp 1988; 21: 93-9.
9. Castro GD, Castro JA: Formación de especies químicas reactivas en la biotransformación de xenobióticos y toxicología. Toxicol 1988; 22: 221-38.
10. De Castro SL: The challenge of Chagas disease chemotherapy. An update of drugs assayed against Trypanosoma cruzi. Acta Trop 1993; 53: 83-98.
11. De Castro SL, Pinto MCFR, Pinto AV: Screening of natural and synthetic drugs against Trypanosona cruzi. 1 Establishing a structure/activity relationship. Microbios 1994; 78: 83-90.
12. Stoppani AOM, Paulino M, Dubin M: Oxygen radicals and the chemotherapy of Chagas disease: an overview. Ciência e Cultura 1996; 48: 75-85.
13. Frayha GJ, Smyth JD, Gobert JG, Savel J: The mechanisms of action of antiprotozoal and anthelmintic drugs in man. Gen Pharmac 1997; 28: 273-99.
14. Haberkorn A, Gönnert R: Animal experimental investigations in the activity of nifurtimox against Trypanosoma cruzi. Arzneim Forsch/Drug Res 1972; 22: 1570-81.
15. Polak A, Richle R: Mode of action of the 2-nitroimidazole derivative benznidazole. Ann Trop Med Parasitol 1978; 72: 45-54.
16. Cichero JA, Segura E, Quatrochi JC: Evolución clínico-parasitológica y tolerancia a la droga de 33 niños con infección chagásica crónica tratados con Bay 2502. Bol Chil Parasitol 1969; 24: 59-62.
17. Lugones HS, Peralta F, Canal Feijóo DC, De Marteleur AEA: Evolucion de la sintomatologia clinica y la funcion hepatica en la enfermedad de Chagas agudo tratada con Bay 2502. Bol Chil Parasitol 1969; 24: 19-24.
18. Cerisola JA: Evolucion serologica de pacientes con enfermedad de Chagas agudo tratados con Bay 2502. Bol Chil Parasitol 1969; 24: 54-9.
19. Prata A, Macedo V, Santos I, Cerisola JA, Silva N: Tratamento da doença de Chagas pelo nifurtimox (Bayer 2502). Rev Soc Brasil Med Trop 1975; 6: 297-308.
20. Cançado JR, Salgado AA, Batista SM, Chiari C: Segundo ensaio terapêutico com o nifurtimox na doença de Chagas. Revista Goiana de Medicina 1976; 22: 203-33.
21. Viotti R, Vigliano C, Armenti H, Segura E: Treatment of chronic Chagas disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up. Am Heart J 1994; 127: 151-62.
22. Segura MA, Molina de Raspi E, Basombrio MA: Reversibility of muscle and heart lesions in chronic, Trypanosoma cruzi infected mice after late trypanomicidal treatment. Mem Inst Oswaldo Cruz 1994; 89: 213-6.
23. Dictar M, Sinagra A, Verón MT, Luna C, Dengra C, De Rissio A, et al: Recipients and donors of bone marrow transplants suffering from Chagas disease: management and preemptive therapy of parasitemia. Bone Marrow Transpl 1998; 21: 391-3.
24. Neal RA, van Bueren J: Comparative studies of drug susceptibility of five strains of Trypanosoma cruzi in vivo and in vitro. Trans R Soc Trop Med Hyg 1988; 82: 709-14.
25. Andrade V, Brodskyn C, Andrade SG: Correlation between isoenzyme patterns and biological behaviour of different strains of Trypanosoma cruzi. Trans R Soc Trop Med Hyg 1983; 77: 796-9.
26. Andrade SG, Rassi A, Magalhaes JB, Filho FF, Luquetti AO: Specific chemotherapy of Chagas disease: a comparison between the response in patients and experimental animals inoculated with the same strain. Trans R Soc Trop Med Hyg 1992; 86: 624-6.
27. Murta SMF, Gazzinelli RT, Brener Z, Romanha AJ: Molecular characterization of susceptible and naturally resistant strains of Trypanosoma cruzi to benznidazole and nifurtimox. Mol Biochem Parasitol 1998; 93: 203-14.
28. Murta SMF, Romanha AJ: In vivo selection of a population of Trypanosoma cruzi and clones resistant to benznidazole. Parasitol 1998; 116: 165-71.
29. Nirdé P, Larroque C, Barnabé C: Drug-resistant epimastigotes of Trypanosoma cruzi and persistence of this phenotype after differentiation into amastigotes. CRAcadSciParis, Sciences de la vie 1995; 318: 1239-44.
30. Nozaki T, Engel JC, Dvorak JA: Cellular and molecular biological analyses of nifurtimox resistance in Trypanosoma cruzi. Am J Trop Med Hyg 1996; 55: 111-7.
31. Marra UD: Comparación de la tolerancia medicamentosa de la nitrofurazona, levofuraltadona y el preparado Bay 2502. Bol Chil Parasitol 1969; 24: 38-42.
32. Laplumé H, Barousse AP, Cabrera H: Efectos indeseables de Nifurtimox y Benznidazol. Medicina (Buenos Aires) 1982; 42: 223.
33. Castro JA, Diaz de Toranzo EG: Toxic effects of nifurtimox and benznidazole, two drugs used against American trypanosomiasis (Chagas Disease). Biomed Environ Sci 1988; 1: 19-33.
34. Nagel R, Nepomnaschy I: Mutagenicity of 2 anti-chagasic drugs and their metabolic deactivation. Mutat Res 1983; 117: 237-42.
35. Nagel R: Genotoxicity studies with two antichagasic drugs. Mutat Res 1987; 191: 17-20.
36. Alejandre-Durán E, Claramunt RM, Sanz D, Vilaplana MJ, Molina P, Pueyo C: Study on the mutagenicity of nifurtimox and eight derivatives with the L-arabinose resistance test of Salmonella typhimurium. Mutat Res 1988; 206: 193-200.
37. González-Martin G, Ponce G, Inostroza V, González M, Paulos C, Guevara A: The disposition of nifurtimox in the rat isolated perfused liver: effect of dose size. J Pharm Pharmacol 1993; 45: 72-4.
38. Docampo R, Mason P, Mottley C, Muniz RPA: Generation of free radicals induced by nifurtimox in mammalian tissues. J Biol Chem 1981; 256: 10930-3.
39. Moreno SNJ, Mason RP, Docampo R: Reduction of nifurtimox and nitrofurantoin to free radical metabolites by rat liver mitochondria. J Biol Chem 1984; 259: 6298-305.
40. Moreno SNJ, Docampo R, Mason RP, Leon W, Stoppani AOM: Different behaviors of benznidazole as free radical generator with mammalian and Trypanosoma cruzi microsomal preparations. Arch Biochem Biophys 1982; 218: 585-91.
41. Masana M, de Toranzo EGD, Castro JA: Reductive metabolism and activation of benznidazole. Biochem Pharmacol 1984; 33: 1041-5.
42. Masana M, Toranzo EGD, Castro JA: Studies on nifurtimox nitroreductase in liver and other rat tissues. Arch Int Pharmacodyn Ther 1984; 270: 4-10.
43. Castro GD, Lopez A, Castro JA: Evidence for hydroxyl free radical formation during paraquat but not for nifurtimox liver microsomal biotransformation. A dimethyl-sulfoxide scavenging study. Arch Toxicol 1988; 62: 355-8.
44. Docampo R, Dubin M, Martino EE, Moreno SNJ, Stoppani AOM: Influencia del nifurtimox sobre el contenido en glutation del higado y de la bilis en la rata. Medicina (Buenos Aires) 1983; 43: 33-40.
45. Dubin M, Moreno SNJ, Martino EE, Docampo R, Stoppani AOM: Increased biliary secretion and loss of hepatic glutathione in rat liver after nifurtimox treatment. Biochem Pharmacol 1983; 32: 483-7.
46. Dubin M, Goijman SG, Stoppani AOM: Effect of nitroheterocyclic drugs on lipid peroxidation and glutathione content in rat liver extract. Biochem Pharmacol 1984; 33: 3419-23.
47. Docampo R, Moreno SNJ, Stoppani AOM: Nitrofuran enhancement of microsomal electron transport, superoxide anion production and lipid peroxidation. Arch Biochem Biophys 1931; 207: 316-24.
48. Castro GD, Castro JA: Studies on pentane evolution by rats treated with nifurtimox or benznidazole. Toxicology 1985; 35: 319-26.
49. Bernacchi AS, de Castro CR, de Toranzo EGD, Castro JA: Effects of nifurtimox or benznidazole administration on rat testes: ultrastructural observations and biochemical studies. Exp Mol Pathol 1986; 45: 245-56.
50. de Castro CR, de Toranzo EGD, Bernacchi AS, Carbone M, Castro JA: Ultrastructural alterations in ovaries from nifurtimox or benznidazole-treated rats: their relation to ovarian nitroreductive biotransformation of both drugs. Exp Mol Pathol 1989; 50: 385-97.
51. de Castro CR, de Toranzo EGD, Carbone M, Castro JA: Ultrastructural effects of nifurtimox on rat adrenal cortex related to reductive biotransformation. Exp Mol Pathol 1990; 52: 98-108.
52. de Castro CR, Diaz de Toranzo EG, Castro JA: Benznidazole-induced Ultrastructural alterations in rat adrenal cortex. Mechanistic studies. Toxicology 1992; 74: 223-32.
53. Gorla N, Díaz Gómez MI, Castro JA: Interaction of benznidazole reactive metabolites with rat liver deoxyribonucleic acid and nuclear proteins. Arch Int Pharmacodyn Ther 1986; 280: 22-31.
54. Flores-Vieira CLL, Barreira AA: Experimental benznidazole encephalopathy: clinical-neurological alterations. J Neurol Sci 1997; 150: 3-11.
55. Flores-Vieira CLL, Chimelli L, Fernandes RMF, Barreira AA: Experimental benznidazole encephalopathy: electroencephalographic and morphological alterations. J Neurol Sci 1997; 150: 13-25.
56. Moya PR, Trombotto GT: Enfermedad de Chagas: efecto clastogenico de nifurtimox y benznidazol en niños. Medicina (Buenos Aires) 1988; 48: 487-91.
57. Teixeira ARL, Calixto MA, Teixeira ML: Chagas disease: carcinogenic activity of the antitrypanosomal nitroarenes in mice. Mutat Res 1994; 305: 189-96.
58. Gugliotta JL, Tanowitz HB, Wittner M, Soeiro R: Trypanosoma cruzi: inhibition of protein synthesis by nitrofuran SQ 18,506. Exp Parasitol 1980; 49: 216-24.
59. Goijman SG, Stoppani AOM: Effects of nitroheterocyclic drugs on macromolecule synthesis and degradation in Trypanosoma cruzi. Biochem Pharmacol 1985; 34: 1331-6.
60. Goijman SG, Frasch ACC, Stoppani AOM: Damage of Trypanosoma cruzi deoxyribonucleic acid by nitroheterocyclic drugs. Biochem Pharmacol 1985; 34: 1457-61.
61. Gonzalez NS, Cazzulo JJ: Effects of trypanocidal drugs on protein biosynthesis in vitro and in vivo by Trypanosoma cruzi. Biochem Pharmacol 1989; 38: 2873-7.
62. González-Martin G, Paulos C, Guevara A, Ponce G: Disposition of nifurtimox and metabolite activity against Trypanosoma cruzi using rat isolated perfused liver. J Pharm Pharmacol 1994; 46: 356-9.
63. Docampo R, Stoppani AOM: Generation of superoxide anion and hydrogen peroxide induced by nifurtimox in Trypanosoma cruzi. Arch Biochem Biophys 1979; 197: 317-21.
64. Sims P, Gutteridge WE: Mode of action of a 5-nitrofuran drug (SQ18506) against Trypanosoma cruzi. Int J Parasitol 1979; 9: 61-7.
65. Youngman RJ, Osswald WF, Elstner EF: Crypto - OH radical production by nitrofurantoin. Biochem Pharmacol 1982; 31: 603-6.
66. Kedderis GL, Miwa GT: The metabolic activation of nitroheterocyclic therapeutic agents. Drug Metab Rev 1988; 19: 33-62.
67. Ames JR, Ryan MD, Kovacic P: Mechanism of antibacterial action: Electron transfer and oxy radicals. Free Radical Biol Med 1986; 2: 377-91.
68. Edwards DI: Nitroimidazole drugs-action and resistance mechanisms.I.Mechanisms of action. J Antimicrob Chemother 1993; 31: 9-20.
69. Edwards DI: Nitroimidazole drugs-action and resistance mechanisms.II.Mechanisms of resistance. J Antimicrob Chemother 1993; 31: 201-10.
70. Docampo R, Moreno SNJ, Stoppani AOM, Leon W, Cruz FS, Villalta F, et al: Mechanism of nifurtimox toxicity in different forms of Trypanosoma cruzi. Biochem Pharmacol 1981; 30: 1947-51.
71. Sreider CM, Grinblat L, Stoppani AOM: Catalysis of nitrofuran redox-cycling and superoxide anion production by heart lipoamide dehydrogenase. Biochem Pharmacol 1990; 40: 1849-57.
72. Grinblat L, Sreider CM, Stoppani AOM: Superoxide anion production by lipoamide dehydrogenase redox-cycling: effect of enzyme modifiers. Biochem Int 1991; 23: 83-92.
73. Grinblat L, Sreider CM, Stoppani AOM: Nitrofuran inhibition of yeast and rat tissue glutathione reductase. Biochem Pharmacol 1989; 38: 767-72.
74. Boveris A, Stoppani AOM: Hydrogen peroxide generation in Trypanosoma cruzi. Experientia 1977; 33: 1306-1308.
75. Boveris A, Sies H, Martino EE, Docampo R, Turrens JF, Stoppani AOM: Deficient metabolic utilization of hydrogen peroxide in Trypanosomoa cruzi. Biochem J 1980; 188: 643-8.
76. Chance B, Sies H, Boveris A: Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979; 59: 527-605.
77. Kedderis GL, Argenbright LS, Miwa GT: Covalent interaction of 5-nitroimidazoles with DMA and protein in vitro: mechanism of reductive activation. Chem Res Toxicol 1989; 2: 146-9.
78. Nieto M, Claramunt RM, Basombrio MA, Stoppani AOM: Essential role of the tetrahydrothiazine group of nifurtimox for activity on Trypanosoma cruzi in mice. Rev Arg Microbiol 1991; 23: 200-3.
79. Mester B, Claramunt RM, Elguero J: NMR studies in the heterocyclic series XXX-Carbon-13 NMR study of 5-nitrofurfural derivatives. Magn Reson Chem 1987; 25: 737-9.
80. Mester B, Elguero J, Claramunt RM, Castanys S, Mascaro ML, Osuna A, et al: Activity against (iTrypanosoma cruzi) of new analogues of nifurtimox. Arch Pharm (Weinheim) 1987; 320: 115-20.
81. Mester B, Hikichi N, Hansz M, Paulino de Blumenfeld M: Quantitative structure activity relationships of 5-nitrofuran derivatives. Chromatographia 1990; 30: 191-4.
82. Mester B, Claramunt RM, Elguero J, Atienza J, Gomaz Ba-rrio A, Escario JA: Research for new antichagasic drugs. Chem Pharm Bull Tokyo 1991; 39: 1990-3.
83. Cerecetto H, Mester B, Onetto S, Seoane G: Formal potentials of new analogues of nifurtimox: relationship to activity. Farmaco 1992; 47: 1207-13.
84. Caracelli I, Stamato FMLG, Mester B, Paulino M, Cerecetto H: A new analogue of nifurtimox. Acta Cryst 1996; C52: 1281-2.
85. Fernández Villamil SH, Dubin M, Brusa MA, Durán RP, Perissinotti LJ, Stoppani AOM: Generation of radical anions of nifurtimox and related nitrofuran compounds by ascorbate. Free Rad Res Comms 1990; 10: 351-60.
86. Paulino-Blumenfeld M, Hansz M, Hikichi N, Stoppani AO M: Electronic properties and free radical production by nitrofuran compounds. Free Rad Res Comms 1992; 16: 207-15.
87. Abitbol R, Boris E, Pinlats E, Podesta D, Maranon J, Gori C: Accion terapeutica de la anfotericina B en la enfermedad de Chagas aguda. Bol Chil Parasitol 1964; 19: 132-4.
88. Docampo R, Moreno SNJ, Turrens JF, Katzin AM, Gonzalez-Cappa SM, Stoppani AOM: Biochemical and ultrastructural alterations produced by miconazole and econazole in Trypanosoma cruzi. Mol Biochem Parasitol 1981; 3: 169-80.
89. McCabe RE, Remington JS, Araujo FG: Ketoconazole inhibition of intracellular multiplication of Trypanosoma cruzi and protection of mice against lethal infection with the organism. J Infect Dis 1984; 150: 594-601.
90. McCabe RE, Remington JS, Araujo FG: Ketoconazole promotes parasitological cure of mice infected with Trypanosoma cruzi. Trans R Soc Trop Med Hyg 1987; 81: 613-5.
91. Beach DH, Goad LJ, Holz GG: Effects of ketoconazole on sterol biosynthesis by Trypanosoma cruzi epimastigotes. Biochem Biophys Res Commun 1986; 136: 851-6.
92. Urbina JA, Vivas J, Ramos H, Larralde G, Aguilar Z, Avilán L: Alteration of lipid order profile and permeability of plasma membranes from Trypanosoma cruzi epimastigotes grown in the presence of ketoconazole. Mol Biochem Parasitol 1988; 30: 185,96.
93. Lazardi K, Urbina JA, de Souza W: Ultrastructural alterations induced by two ergosterol biosynthesis inhibitors, ketoconazole and terbinafine, on epimastigotes and amastigotes of Trypanosoma (Schizotrypanum) cruzi. Antimicrob Agents Chemother 1990; 34: 2097-105.
94. Maldonado RA, Molina J, Payares G, Urbina JA: Experimental chemotherapy with combinations of ergosterol biosynthesis inhibitors in murine models of Chagas Disease. Antimicrob Agents Chemother 1993; 37: 1353-9.
95. Brener Z, Cançado JR, Galvao LM, da Luz MP, Filardi L, Pereira ES, et al: An experimental and clinical assay with ketoconazole in the treatment of Chagas' disease. Mem Inst Oswaldo Cruz 1993; 88: 149-53.
96. de Castro SL, Soeiro MNC, Higashi KO, Meirelles MNL: Differential effect of amphotericin B on the three evolutive stages of Trypanosoma cruzi and on the host cell-parasite interaction. Braz J Med Biol Res 1993; 26: 1219-29.
97. Avila JL, Avila A, Polegre MA: Inhibitory effects of sinefungin and its cyclic analog on the multiplication of Trypanosoma cruzi isolates. Am J Trop Med Hyg 1993; 48: 112-9.
98. 24(25)-sterol methyl transferase inhibitors and their combinations with ketoconazole. Mol Biochem Parasitol 1995; 73: 199-210.
99. Abt W, Aguilera X, Arribada A, Perez C, Miranda C, Sanchez G, et al: Treatment of chronic Chagas disease with itraconazole and allopurinol. Am J Trop Med Hyg 1998; 59: 133-8.
100. Urbina JA, Payares G, Molina J, Sanoja C, Liendo A, Lazardi K, et al: Cure of short-and long-term experimental Chagas' disease using D0870. Science 1996; 273: 969-71.
101. Koltin Y, Hitchcock CA: The search for a new triazole antifungal agents. Curr Opin Chem Biol 1997; 1: 176-82.
102. Davies MJ, Ross AM, Gutteridge WE: The enzymes of purine salvage in Trypanosoma cruzi, Trypanosoma brucei and Leishmania mexicana. Parasitol 1983; 87: 211-7.
103. Hammond DJ, Gutteridge WE: Purine and pyrimidine metabolism in the trypanosomatidae. Mol Biochem Parasitol 1984; 13: 243-61.
104. Christopherson RI, Lyons SD: Potent inhibitors of de novo pyrimidine and purine biosynthesis as chemotherapeutic agents. Med Res Rev 1990; 10: 505-48.
105. Spector T, Berens RL, Marr JJ: Adenylosuccinate synthase and adenylosuccinate lyase from Trypanosoma cruzi. Specificity studies with potential chemotherapeutic agents. Biochem Pharmacol 1981; 31: 225-9.
106. Marr JJ, Berens RL, Nelson DJ: Antitrypanosomal effect of allopurinol: conversion n vivo to aminopyrazolo-pyrimidine nucleotides by Trypanosoma cruzi. Science 1978; 201: 1018-20.
107. Avila JL, Avila A: Trypanosoma cruzi: allopurinol in the treatment of mice with experimental acute Chagas disease. Exp Parasitol 1981; 51: 204-8.
108. Berens RL, Marr JJ, Steele da Cruz F, Nelson DJ: Effect of allopurinol on Trypanosoma cruzi: metabolism and biological activity in intracellular and bloodstream forms. Antimicrob Agents Chemother 1982; 22: 657-61.
109. Marr JJ, Berens RL: Pyrazolopyrimidine metabolism in the pathogenic trypanosomatidae. Mol Biochem Parasitol 1983; 7: 339-56.
110. Avila JL, Avila A, Muñoz E, Monzón H: Trypanosoma cruzi: 4-aminopyrazolopyrimidine in the treatment of experimental Chagas' disease. Exp Parasitol 1983; 56: 236-40.
111. Berens RL, Marr JJ, Looker DL, Nelson DJ, LaFon SW: Efficacy of pyrazolopyrimidine ribonucleosides against Trypanosoma cruzi: studies in vitro and in vivo with sensitive and resistant strains. J Infect Dis 1984; 150: 602-11.
112. Avila JL, Avila A, Monzón H: Differences in allopurinol and 4-aminopyrazolo(3,4-d) pyrimidine metabolism in drug-sensitive and insensitive strains of Trypanosoma cruzi. Mol Biochem Parasitol 1984; 44: 51-60.
113. Croft SL, Neal RA: The effect of allopurinol ribonucleoside and formycin B on Trypanosoma cruzi infections in mice. Trans R Soc Trop Med Hyg 1985; 79: 517-8.
114. Guimaaes RC, Gutteridge WE: Uptake of purine bases by Trypanosoma cruzi culture epimastigote. Braz J Med Biol Res 1986; 19: 339-50.
115. Guimaraes RC, Gutteridge WE: Purine base uptake in Trypanosoma cruzi: adaptations and effects of inhibitors. Braz J Med Biol Res 1987; 20: 1-10.
116. Avila JL, Polegre MA, Robins RK: Biological action of pyrazolopyrimidine derivatives against Trypanosoma cruzi. Studies in vitro and in vivo. Comp Biochem Physiol 1987; 86C: 49-54.
117. Avila JL, Rojas T, Avila A, Polegre MA, Robins RK: Biological activity of analogs of guanine and guanosine against american Trypanosoma and Leishmania spp. Antimicrob Agents Chemother 1987; 31: 447-51.
118. Avila JL, Avila A: Defective transport of pyrazolopyrimidine ribosides in insensitive Trypanosoma cruzi wild strains is a parasite-stage specific and reversible characteristic. Comp Biochem Physiol 1987; 87B: 489-95.
119. Gonzalez AM, Castanys S, Osuna A: Inhibitory effect of new pyrimidine bases on Trypanosoma cruzi. Arch Pharm (Weinheim) 1988; 322: 843-6.
120. van Bueren J, Cenini P, Neal RA: Effect of nifurtimox or benznidazole on the uptake of radioactive hypoxanthine by blood stream trypamastigotes of Trypanosoma cruzi. Med Sci Res 1988; 16: 1207-8.
121. Gallerano RH, Marr JJ, Sosa RR: Therapeutic efficacy of allopurinol in patients with chronic Chagas' disease [published erratum]. Am J Trop Med Hyg 1991; 44: 580.
122. Nakajima-Shimada J, Hirota Y, Oaki T: Inhibition of Trypanosoma cruzi growth in mammalian cells by purine and pyrimidine analogs. Antimicrob Agents Chemother 1996; 40: 2455-8.
123. Eakin AE, Guerra A, Focia PJ, Torres-Martinez J, Craig III SP: Hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi as a target for structure-based inhibitor design: crystallization and inhibition studies with purine analogs. Antimicrob Agents Chemother 1997; 41: 1686-92.
124. Bontempi E, Franke de Cazzulo BM, Ruiz AM, Cazzulo JJ: Purification and properties of an acidic protease from epimastigotes of Trypanosoma cruzi. Comp Biochem Physiol 1984; 77B: 599-604.
125. Ashall F, Angliker H, Shaw E: Lysis of trypanosomes by peptidyl fluoromethyl ketones. Biochem Biophys Res Commun 1990; 170: 923-9.
126. Meirelles MN, Juliano L, Carmona E, Silva SG, Costa EM, Murta ACM, et al: Inhibitors of the major cysteinyl proteinase (GP57/51) impair host cell invasion and arrest the intracellular development of Trypanosoma cruzi in vitro. 1992; 52: 175-84.
127. Harth G, Andrews N, Mills AA, Engel JC, Smith R, McKerrow JH: Peptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi. Mol Biochem Parasitol 1993; 58: 17-24.
128. Mc Kerrow JH, McGrath ME, Engel JC: The cysteine proteases of Trypanosoma cruzi as a model for antiparasite drug design. Parasitol Today 1995; 11: 279-82.
129. Engel JC, Doyle PS, Palmer J, Hsieh I, Bainton DF, McKerrow JH: Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi. J Cell Sci 1998; 111: 597-606.
130. Engel JC, Doyle PS, Hsieh I, McKerrow JH: Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med 1998; 188: 725-34.
131. Zaidi R, Hadi SM: Interaction of gossypol with DNA. Toxicol in Vitro 1992; 6: 71-76.
132. Bugeja V, Charles G, Collier D, Wilkie D: Primary mitochondrial activity of gossypol in yeast and mammalian cells. Biochem Pharmacol 1988; 37: 4217-24.
133. McClarty GA, Chan AK, Creasey DC, Wright JA: Ribonucleotide reductase: an intracellular target for the male antifertility agent, gossypol. Biochem Biophys Res Commun 1985; 133: 303-5.
134. Montamat EE, Burgos C, Gerez de Burgos NM, Rovai LE, Blanco A: Inhibitory of action of gossypol on enzymes and growth of Trypanosoma cruzi. Science 1982; 218: 288-9.
135. Blanco A, Aoki A, Montamat EE, Rovai LE: Effect of gossypol upon motility and ultraestructure of Trypanosoma cruzi. J Protozool 1983; 30: 648-51.
136. Gerez de Burgos NM, Burgos C, Montamat EE, Rovai LE, Blanco A: Inhibition by gossypol of oxidoreductases from Trypanosoma cruzi. Biochem Pharmacol 1984; 33: 955-9.
137. Burgos C, Gerez de Burgos NM, Rovai LE, Blanco A: In vitro inhibition by gossypol of oxidoreductases from human tissues. Biochem Pharmacol 1986; 35: 801-4.
138. Roval LE, Aoki A, Gerez de Burgos NM, Blanco A: Effect of gossypol on trypomastigotes and amastigotes of Trypanosona cruzi. J Protozool 1990; 37: 280-6.
139. Olcina MA, Blanco A: Effects of gossypol on mice infected with Trypanosoma cruzi. Acta Physiol Pharmacol Latinoam 1990; 40: 219-26.
140. D'Albuquerque IL, Maciel MCN, Schuler AR, de Araujo M do C, Medeiros Maciel G, Cavalcanti M da SB, et al: Preparaçao e primeiras observaçoes sobre as propriedades antibióticas e antineoplásicas das naftoquinonas homólogos inferiores na série da 2-hidróxi-3-(3-metil-2-butenil)-1,4-naftoquinona(lapachol). Revta Inst Antibiot Univ Recife 1972; 12: 31-40.
141. Cruz FS, Docampo R, de Souza W: Effect of b-lapachone on hydrogen peroxide production in Trypanosoma cruzi. Acta Trop 1978; 35: 35-40.
142. Lopez JN, Cruz FS, Docampo R, Vasconcellos ME, Sampaio MCR, Pinto AV, et al: 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 1978; 72: 523-31.
143. Docampo R, Lopes JN, Cruz JS, De Souza W: Trypanosoma cruzi: ultrastructural and metabolic alterations of epimastigotes by β-lapachone. Exp Parasitol 1977; 42: 142-9.
144. Molina Portela MP, Pahn EM de, Galeffi C, Stoppani AOM: Efecto de orto-naftoquinonas lipofílicas sobre el crecimiento y la producción de peróxidos por Leptomonas seymouri y Crithidia fasciculata. Rev Arg Microbiol 1991; 23: 1-14.
145. Molina Portela MP, Fernandez Villamil SH, Perissinotti LJ, Stoppani AOM: Redox cycling of o-naphthoquinones in trypanosomatids. Superoxide and hydrogen peroxide production. Biochem Pharmacol 1996; 52: 1875-82.
146. Schaffner-Sabba K, Schmidt-Ruppin KH, Wehrli W, Schuerch AR, Wasley JWF: b-lapachone: synthesis of derivatives and activities in tumor models. J Med Chem 1984; 27: 990-4.
147. Boveris A, Docampo R, Turrens JF, Stoppani AOM: Effect of b-lapachone on superoxide anion and hydrogen peroxide production by Trypanosoma cruzi. Biochem J 1978; 175: 431-9.
148. Boveris A, Stoppani AOM, Docampo R, Cruz FS: Superoxide anion production and trypanocidal action of naphthoquinones on Trypanosoma cruzi. Comp Biochem Physiol 1973; 61C: 327-9.
149. Molina Portela MP, Stoppani AOM: Redox cycling of b-lapachone in the presence of dihydrolipoamide and oxygen. Biochem Pharmacol 1996; 51: 275-83.
150. Fernández Villamil SH, Dubin M, Galeffi C, Stoppani AOM: Effects of mansonones on lipid peroxidation, P-450 monooxygenase activity, and superoxide anion generation by rat liver microsomes. Biochem Pharmacol 1990; 40: 2343-51.
151. Goijman SG, Turrens JF, Marini-Bettolo GB, Stoppani AOM: Effect of tingenone, a quinonoid triterpene on growth and macromolecule biosynthesis in Trypanosoma cruzi. Experientia 1985; 41: 646-8.
152. Schwarcz de Tarlovsky MN, Goijman SG, Molina Portela MP, Stoppani AOM: Effect of isoxazolyl naphthoquinoneimines on growth and oxygen radical production by Trypanosoma cruzi and Crithidia fasciculata. Experientia 1990; 46: 502-5.
153. Goijman SG, Stoppani AOM: Effects of b-lapachone, a peroxide-generating quinone, on macromolecule synthesis and degradation in Trypanosoma cruzi. Arch Biochem Biophys 1985; 240: 273-80.
154. Dubin M, Fernandez Villamil SH, Stoppani AOM: Inhibition of microsomal lipid peroxidation and cytochrome P-450-catalyzed reactions by b-lapachone and related naphthoquinones. Biochem Pharmacol 1990; 39: 1151-60.
155. Fernández Villamil SH, Dubin M, Molina Portela MP, Perissinotti LJ, Brusa MA, Stoppani AOM: Semiquinone production by lipophilic o-naphthoquinones. Redox Report 1997; 3: 245-52.
156. Li CJ, Averboukh L, Pardee AB: b-lapachone, a novel DNA topoisomerase I inhibitor with a mode of action different from camptothecin. J Biol Chem 1993; 268: 22463-8.
157. Li CJ, Zhang LJ, Dezube BJ, Crumpacker CS, Pardee AB: Three inhibitors of type 1 human immunodeficiency virus long terminal repeat-directed gene expression and virus replication. Proc Natl Acad Sci USA 1993; 90: 1839-42.
158. Degrassi F, De Salvia R, Berghella L: The production of chromosomal alterations by b-lapachone, an activator of topoisomerase I. Mutat Res 1993; 288: 263-7.
159. Boothman DA, Pardee AB: Inhibition of radiation-induced neoplastic transformation by b-lapachone. Proc Natl Acad Sci USA 1989; 86: 4963-7.
160. Boothman DA, Trask DK, Pardee AB: Inhibition of potentially lethal DNA damage repair in human tumor cells by b-lapachone, an activator of topoisomerase I. Cancer Res 1989; 49: 605-612.
161. Planchon SM, Wuerzberger S, Frydman B, Witiak DT, Hutson P, Church DR, et al: β-Lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: A p53-independent response. Cancer Res 1995; 55: 3706-11.
162. Glen VL, Hutson PR, Kehrli NJ, Boothman DA, Wilding G: Quantitation of β-lapachone and 3-hydroxi-b-lapachone in human plasma samples by reversed-phase high-performance liquid chromatography. J Chromatogr 1997; 692: 181-6.
163. Neal RA, van Bueren J, McCoy NG, Iwobi M: Reversal of drug resistance in Trypanosoma cruzi and Leishmania donovani by verapamil. Trans R Soc Trop Med Hyg 1989; 83: 197-8.
164. Tanowitz HB, Morris SA, Weiss LM, Bilezikian JP, Factor SM, Wittner M: Effect of verapamil on the development of chronic experimental Chagas disease. Am J Trop Med Hyg 1989; 41: 643-9.
165. Tanowitz HB, Wittner M, Chen B, Huang H, Weiss LM, Christ GJ, et al: Effects of verapamil on acute murine Chagas' disease. J Parasitol 1996; 82: 814-9.
166. Chabala JC, Waits VB, Ikeler T, Patchett AA, Payne L, Peterson LH, et al: 1-(Substitued)benzyl-5-aminoimidazole-4-carboxamides are potent orally inhibitors of Trypanosoma cruzi in mice. Experientia 1991; 47: 51-3.
167. Croft SL, Snowdon D, Yardley V: The activities of four anticancer alkyllysophospholipids against Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. J Antimicrob Chemother 1996; 38: 1041-7.
168. Kinnamon KE, Poon BT, Hanson WL, Waits VB: Primaquine analogues that are potent anti-Trypanosoma cruzi agents in a mouse model. Ann Trop Med Parasitol 1996; 90: 467-74.
169. Fournet A, Ferreira M-E, Rojas de Arias A, Schinini A, Nakayama H, Torres S, et al: The effect of bisbenzylisoquinoline alkaloids on Trypanosoma cruzi infections in mice. Int J Antimicrobial Agents 1997; 8: 163-70.
170. Kinnamon KE, Poon BT, Hanson WL, Waits VB: Evidence that 8-aminoquinolines are potentially effective drugs against Chagas disease. Ann Trop Med Parasitol 1997; 91: 147-52.
171. Kinnamon KE, Poon BT, Hanson WL, Waits VB: In pursuit of drugs for American Trypanosomiasis: evaluation of some «standards» in a mouse model. Proc Soc Exp Biol Med 1997; 216: 424-8.
172. Kinnamon KE, Poon BT, Hanson WL, Waits VB: Trypanosoma cruzi: a novel chemical class (nitrobenzofurans) active against infections in mice (Mus musculus). Exp Parasitol 1998; 89: 251-6.
173. Brener Z: Chemotherapeutic studies in tissue cultures infected with Trypanosoma cruzi: the mode of action of some active compounds. Ann Trop Med Parasitol 1966; 60: 445.
174. Docampo R, Boiso JF de, Stoppani AOM: Tricarboxylic acid cycle operation at the kinetoplast-mitochondrion complex of Trypanosoma cruzi. Biochim Biophys Acta 1978; 502: 466-76.
175. Docampo R, Cruz FS, Muniz RPA, Esquivel DMS, de Vasconcellos MEL: Generation of free radicals from phenazine methosulfate in Trypanosoma cruzi epimastigotes. Acta Trop 1978; 35: 221-8.
176. Leon L, Vasconcellos ME, Leon W, Cruz FS, Docampo R, de Souza W: Trypanosoma cruzi: effect of olivacine on macromolecular synthesis, ultraestructure, and respiration of epimastigotes. Exp Parasitol 1978; 45: 151-9.
177. Ruiz-Pérez LM, Osuna A, Castanys S, Gamarro F, Craciunescu D, Doadrio A: Evaluation of the toxicity of Rh(III) and Pt(II) complexes against Trypanosoma cruzi culture forms. Arzneim Forsch/Drug Res 1986; 36: 13-6.
178. Ohara A, Alves MJM, Colli W, Filardi LS, Brener Z: Primaquine can mediate hydroxyl radical generation by Trypanosoma cruzi extracts. Biochem Biophys Res Commun 1986; 135: 1029-34.
179. Albonico SM, Assem ME, Benages IA, Montiel AA, Pizzorno MT, Docampo R, et al: Synthetic trypanocides: growth-inhibiting properties of new 1,2,3,4-tetrahydrocarbazoles on Trypanosoma cruzi. Rev Arg Microbiol 1987; 19: 121-4.
180. Ferreira J, Coloma L, Fones E, Letelier ME, Repetto Y, Morello A, et al: Effects of t-butyl-4-hydroxyanisole and other phenolic antioxidants on tumoral cells and Trypanosoma parasites. FEBS Lett 1988; 234: 485-8.
181. Osuna A, Ruiz-Perez LM, Gamarro F, Rodriguez-Santiago JI, Castanys S, Sharples D, et al: New antiparasitic agents. Comparison between trypanocidal activities of some acridine derivatives against Trypanosoma cruzi in vitro. Chemotherapy 1988; 34: 127-33.
182. de Diego C, Avendaño C: Effect of heterocyclic analogues of triphenylmethane dyes against Trypanosoma cruzi. Ann Trop Med Parasitol 1988; 82: 235-41.
183. Alcalde E, Dinarés I, Elguero J, Frigola J, Osuna A, Castanys S: Pyridinium azolate betaines and their derivatives: a new class of antiprotozoal agents. Eur J Med Chem 1990; 25: 309-19.
184. Queiroz da Cruz M, Bräscher HM, Vargens JR, Oliveira-Lima A: Effect of actinomycin D on Trypanosoma cruzi. Experientia 1991; 47: 89-92.
185. Atienza J, Martínez-Díaz RA, Gómez Barrio, Escario JA, Herrero A, Ochoa C, et al: Activity assays of thiadiazine derivatives on Trichomonas vaginalis and amastigote forms of Trypanosoma cruzi. Chemotherapy 1992; 38: 441-6.
186. Yakubu MA, Basso B, Kierszenbaum F: DL-α-difluoromethylarginine inhibits intracellular Trypanosoma cruzi multiplication by affecting cell division but not trypomastigote-amastigote transformation. J Parasitol 1992; 78: 414-9.
187. Fournet A, Muñoz V, Roblot F, Hocquemiller, Cavé A, Gantier J-C: Antiprotozoal activity of dehydrozaluzanin C, a sesquiterpene lactone isolated from Munnozia maronii (Asteraceae). Phytother Res 1993; 7: 111-5.
188. Urbina JA, Marchan E, Lazardi K, Visbal G, Apitz-Castro R, Gil F, et al: Inhibition of phosphatidylcholine biosynthesis and cell proliferation in Trypanosoma cruzi by ajoene, an antiplatelet compound isolated from garlic. Biochem Pharmacol 1993; 45: 2381-7.
189. Rojas de Arias A, Inchausti A, Ascurrat M, Fleitas N, Rodriguez E: In vitro activity and mutagenicity of bisbenzylisoquinolines and quinones against Trypanosoma cruzi trypomastigotes. Phytother Res 1994; 8: 141-4.
190. Messeder JC, Tinoco LW, Figueroa-Villar JD, Souza EM, Santa Rita R, de Castro SL: Aromatic guanyl hydrazones: synthesis, structural studies and n vitro activity against Trypanosoma cruzi. Bioorg Medicinal Chem Letter 1995; 5: 3079-84..
191. Alves TMA, Chaves PPG, Santos LMST, Nagem TJ, Murta SMF, Ceravolo IP, et al: A diterpene from Mikania obtusata active on Trypanosoma cruzi. Planta Med 1995; 61: 85-6.
192. Rodrigues RR, Lane JE, Carter CE, Bogitsh BJ, Singh PK, Zimmerman LJ, et al: Chelating agent inhibition of Trypanosoma cruzi epimastigotes In vitro. J Inorg Biochem 1995; 60: 227-88.
193. Gottlieb P, Margolis-Nunno H, Robinson R, Shen L-G, Chimezie E, Horowitz B, et al: Inactivation of Trypanosoma cruzi trypomastigote forms in blood components with a psoralen and ultraviolet A light. Photochem Photobiol 1996; 63: 562-5.
194. Rodriguez JB, Zhong L, Docampo R, Gross EG: Biological evaluation of two potent inhibitors of Trypanosoma cruzi epimastigotes against the intracellular form of the parasite. Bioorg Medicinal Chem Letter 1996; 6: 2783-6.
195. de Oliveira AB, Saúde DA, Perry KSP, Duarte DS, Raslan DS, Boaventura MAD, et al: Trypanocidal sesquiterpenes from Lychnophora species Phytother Res 1996; 10: 292-5.
196. de Conti R, Santa Rita RM, de Souza EM, Melo PS, Haun M, de Castro SL, et al: In vitro trypanocidal activities of a novel series of N,N-dimethyl-2-propen-1-amine derivative. Microbios 1996; 85: 83-7.
197. Schvartzapel AJ, Zhong L, Docampo R, Rodriguez JB, Gros EG: Design, synthesis, and biological evaluation of new growth inhibitors of Trypanosoma cruzi (epimastigotes). J Med Chem 1997; 40: 2314-22
198. Gamage S, Figgitt DP, Wojcik SJ, Ralph RK, Ransijn A, Mauel J, et al: Structure-activity relationships for the antileishmanial and antitrypanosomal activities of 1'-substituted 9-anilinoacridines. J Med Chem 1997; 40: 2634-42.
199. Canto-Cavalheiro MM, Echevarria A, Araujo CAC, Bravo MF, Santos LHS, Jansen AM, et al: The potential effects of new synthetic drugs against Leishmania amazonensis and Trypanosoma cruzi. Microbios 1997; 90: 51-60.
200. Franke de Cazzulo BM, Bernacchi A, Esteva MI, Ruiz MA, Castro JA, Cazzulo JJ: Trypanocidal effect of SKF525A, proadifen, on different developmental forms of Trypanosoma cruzi. Medicina (Buenos Aires) 1998; 58: 415-8.
201. Fairlamb AH, Cerami A: Metabolism and functions of trypanothione in the kinetoplastida. Annu Rev Microbiol 1992; 46: 695-729.
202. Sullivan FX, Walsh CT: Cloning, sequencing, overproduction and purification of trypanothione reductase from Trypanosoma cruzi. Mol Biochem Parasitol 1991; 44: 145-8.
203. Walsh C, Bradley M, Nadeau K: Molecular studies on trypanothione reductase, a target for antiparasitic drugs. Trends Biochem Sci 1991; 16: 305-9.
204. Schirmer RH, Müller JG, Krauth-Siegel L: Disulfide-reductase inhibitors as chemotherapeutic agents: the design of drugs for trypanosomiasis and malaria. Angew Chem Int Ed Engl 1995; 34: 141-54.
205. Krauth-Siegel RL, Schöneck R: Trypanothione reductase and lipoamide dehydrogenase as targets for a structure-based drug design. FASEB J 1995; 9: 1138-46.
206. Carnieri EGS, Moreno SNJ, Docampo R: Trypanothione-dependent peroxide metabolism in Trypanosoma cruzi different stages. Mol Biochem Parasitol 1993; 61: 79-86.
207. Henderson GB, Ulrich P, Fairlamb AH, Rosenberg I, Pereira M, Sela M, et al: «Subversive» substrates for the enzyme trypanothione disulphide reductase: alternative approach to chemotherapy of Chagas' disease. Proc Natl Acad Sci USA 1988; 85: 5374-5378
208. Jakoby EM, Schlichting I, Lantwin CB, Kabsch W, Krauth-Siegel RL: Crystal structure of the Trypanosoma cruzi trypanothione reductase-mepacrine complex. Protein-Struct Funct Genet 1996; 24: 73-80.
209. O'Sullivan MC, Dalrymple DM, Zhou Q: Inhibiting effects of spermidine derivatives on Trypanosoma cruzi trypanothione reductase. J Enzym Inhib 1996; 11: 97-114.
210. Gocke E: Review of the genotoxic properties of chlorpromazine and related phenothiazines. Mutat Res 1996; 366: 9-21.
211. Seebeck D, Gehr P: Trypanocidal action of phenothiazines in Trypanosoma brucei. Mol Biochem Parasitol 1983; 9: 197-208.
212. Garforth J, Yin H, McKie JH, Douglas KT, Fairlamb AH: Rational design of selective ligands for trypanothione reductase from Trypanosoma cruzi. Structural effects on the inhibition by dibenzazepines based on imipramine. J Enzym Inhib 1997; 12: 161-73.
213. Chan C, Yin H, Garforth J, McKie JH, Jaouhari R, Speers P, et al: Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs. J Med Chem 1998; 41: 148-56.
214. Fernandez AR, Fretes R, Rubiales S, Lacuara JL, Paglini-Oliva P: Trypanocidal effects of promethazine. Medicina (Buenos Aires) 1997; 57: 59-63.
215. Lacuara JL, de Barioglio SR, de Oliva PP, Bernacchi AS, de Culasso AF, Castro JA, et al: Disruption of mitochondrial function as the basis of the trypanocidal effect of trifluoperazine on Trypanosoma cruzi. Experientia 1991; 47: 612-6.
216. 2--dependent and oxidative cell injury. Biochem Pharmacol 1994; 48: 1509-17.
217. Jeding I, Evans PJ, Akanmu D, Dexter D, Spencer JD, Aruoma CI, et al: Characterization of the potential antioxidant and pro-oxidant actions of some neuroleptic drugs. Biochem Pharmacol 1995; 49: 359-65.
218. Chen S, Lin C-H, Kwon DS, Walsh CT, Coward JK: Design, synthesis and biochemical evaluation of phosphonate and phosphonamidate analogs of glutathionylspermidine as inhibitors of glutathionylspermidine synthetase/amidase from Escherichia coli. J Med Chem 1997; 40: 3842-50
219. Travis AS: Paul Ehrlich: a hundred years of chemotherapy 1891-1991. In: London the Biochemist, (ed.), The Biochemical Society 1991; pp. 9-12.
220. Wang CC: Validating targets for antiparasite chemotherapy. Parasitol 1997; 114: S31-S44.
221. Verlinde CLMJ, Hol WGJ: Structure-based drug design: progress, results and challenges. Structure 1994; 2: 577-87.