The trypanocidal activity of naphthoquinones: A review

Molecules

Volumn 14, Issue 11, 2009, Pages 4570-4590

  Pinto, Antônio Ventura ^a   De Castro, Solange Lisboa ^b  

^a FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

^b INSTITUTO OSWALDO CRUZ   (Brazil)

Author keywords

lapachone; Chagas disease; Naphthoquinones; Trypanosoma cruzi

Indexed keywords

ANTITRYPANOSOMAL AGENT; BETA LAPACHONE; BETA-LAPACHONE; NAPHTHOQUINONE;

ANIMAL; CHAGAS DISEASE; DRUG EFFECT; HUMAN; PARASITOLOGY; REVIEW; TRYPANOSOMA CRUZI;

ANIMALS; CHAGAS DISEASE; HUMANS; NAPHTHOQUINONES; TRYPANOCIDAL AGENTS; TRYPANOSOMA CRUZI;

EID: 73349111624     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules14114570     Document Type: Review

References (126)

1. Newman, D. J.; Cragg, G. M.; Snader, K. M. The influence of natural products upon drug discovery. Nat. Prod. Rep. 2000, 17, 215-234.
2. Ernst, E. The efficacy of herbal medicine: An overview. Fundam. Clin. Pharmacol. 2005, 19, 405-409.
3. Soejarto, D. D.; Farnsworth, N. R. Tropical rain forests: Potential source of new drugs? Perspect. Biol. Med. 1989, 32, 244-256.
4. Raskin, I.; Ribnicky, D. M.; Komarnytsky, S.; Ilic, N.; Poulev, A.; Borisjuk, N.; Brinker, A.; Moreno, D. A.; Ripoll, C.; Yakoby, N.; O'Neal, J. M.; Cornwell, T.; Pastor, I.; Fridlender, B. Plants and human health in the twenty-first century. Trends Biotechnol. 2002, 20, 522-531.
5. Foster, B. C.; Arnason, J. T.; Briggs, C. J. Natural health products and drug disposition. Annu. Rev. Pharmacol. Toxicol. 2005, 45, 203-226.
6. Horton, D. A.; Bourne, G. T.; Smythe, M. L. The combinatorial synthesis of bicyclic privileged structures or privileged substructures. Chem. Rev. 2003, 103, 893.
7. Newman, D. J.; Cragg, G. M. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod. 2007, 70, 461-477.
8. Butler, M. S. Natural products to drugs: Natural product-derived compounds in clinical trials. Nat. Prod. Rep. 2008, 25, 475-516.
9. Tagboto, S.; Townson, S. Antiparasitic properties of medicinal plants and other naturally occurring products. Adv. Parasitol. 2001, 50, 199-295.
10. Constantino, L.; Barlocco, D. Privileged structures as leads in medicinal chemistry. Curr. Med. Chem. 2006, 13, 65-85.
11. Powis, G. Metabolism and reactions of quinoid anticancer agents. Pharmacol. Ther. 1987, 35, 57-162.
12. O'Brien, P. J. Molecular mechanisms of quinone cytotoxicity. Chem. Biol. Interact. 1991, 80, 1-41.
13. Abreu, F. C.; Ferraz, P. A.; Goulart, M. O. Some applications of electrochemistry in biomedical chemistry. Emphasis on the correlation of electrochemical and bioactive properties. J. Braz. Chem. Soc. 2002, 13, 19-35.
14. Hillard, E. A.; Abreu, F. C.; Ferreira, D. C.; Jaouen, G.; Goulart, M. O.; Amatore, C. Electrochemical parameters and techniques in drug development, with an emphasis on quinones and related compounds. Chem. Commun. 2008, 23, 2612-2628.
15. Arenas, P. Medicine and magic among the Maka Indians of the Paraguayan Chaco. J. Ethnopharmacol. 1987, 21, 279-295.
16. Bastien, J. W. Pharmacopeia of Qollahuaya Andeans. J. Ethnopharmacol. 1983, 8, 97-111.
17. Hazra, B.; Das Sarma, M.; Sanyal, U. Separation methods of quinonoid constituents of plants used in Oriental traditional medicines. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2004, 812, 259-275.
18. Vilamil-Fernandez, S.; Stoppani, A. O.; Dubin, M. Redox cycling of β-lapachone and structural analogues in microsomal and cytosol liver preparations. Methods Enzymol. 2004, 378, 67-87.
19. Ross, D.; Siegel, D. 2004. NAD (P) H: Quinone oxidoreductase 1 (NQO1, DT-diaphorase), functions and pharmacogenetics. Methods Enzymol. 2004, 382, 115-144.
20. Munday, R.; Smith, B. L.; Munday, C. M. Structure-activity relationships in the haemolytic activity and nephrotoxicity of derivatives of 1, 2-and 1, 4-naphthoquinone. J. Appl. Toxicol. 2007, 27, 262-269.
21. Munday, R. Autoxidation of naphtohydroquinones: Effects of pH, naphthoquinones and superoxide dismutase. Free Rad. Res. 2000, 32, 245-253.
22. Monks, T. J.; Jones, D. C. The metabolism and toxicity of quinones, quinonimines, quinone methides, and quinone-thioethers. Curr. Drug Metab. 2002, 3, 425-438.
23. Bolton, J. L.; Trush, M. A.; Penning, T. M.; Dryhurst, G.; Monks, T. J. Role of quinones in toxicology. Chem. Res. Toxicol. 2000, 13, 135-160.
24. Brunmark, A.; Cadenas, E. Redox and addition chemistry of quinoid compounds and its biological implications. Free. Rad. Biol. Med. 1989, 7, 435-477.
25. Monks, T. J.; Hanslik, R. P.; Cohen, G. M.; Ross, D.; Graham, D. G. Quinone chemistry and toxicity. Toxicol. Appl. Pharmacol. 1992, 112, 2-16.
26. Goulart, M. O.; Falkowski, P.; Ossowski, T.; Liwo, A. Electrochemical study of oxygen interaction with lapachol and its radical anions. Bioelectrochemistry 2003, 59, 85-87.
27. Vilamil-Fernandez, S.; Stoppani, A. O.; Dubin, M. Redox cycling of β-lapachone and structural analogues in microsomal and cytosol liver preparations. Methods Enzymol. 2004, 378, 67-87.
28. Hussain, H.; Krohn, K.; Uddin Ahmad, V. U.; Miana, G. A.; Greend, I. R. Lapachol: An overview. Arkivoc 2007, 2, 145-171.
29. Santana, C. F.; Lima, O.; d'Albuquerque, I. L.; Lacerda, A. L.; Martins, D. G. Antitumoral and toxicological properties of extracts of bark and various wood components of pau d'arco (Tabebuia avellanedae). Rev. Inst. Antibiot. 1968, 8, 89-94
30. Li, C. J.; Wang, C.; Pardee, A. B. Induction of apoptosis by β-lapachone in human prostate cancer cells. Cancer Res. 1995, 55, 3712-3715.
31. Planchon, S. M.; Wuerzberger, S.; Frydman, B.; Witiak, D. T.; Hutson, P.; Church, D. R.; Wilding, G.; Boothman, D. A. β-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: A p53-independent response. Cancer Res. 1995, 55, 3706-3711.
32. Wuerzberger, S. M.; Pink, J. J.; Planchon, S. M.; Byers, K. L.; Bornmann, W. G.; Boothman, D. A. Induction of apoptosis in MCF-7: WS8 breast cancer cells by β-lapachone. Cancer Res. 1998, 58, 1876-1885.
33. Dubin, M.; Fernandez Villamil, S. H.; Stoppani, A. O. Cytotoxicity of β-lapachone, a naphthoquinone with possible therapeutic use. Medicina 2001, 61, 343-350.
34. Planchon, S. M.; Pink, J. J.; Tagliarino, C.; Bornmann, W. G.; Varnes, M. E.; Boothman, D. A. β-Lapachone-induced apoptosis in human prostate cancer cells: Involvement of NQO1/xip3. Exp. Cell. Res. 2001, 267, 95-106.
35. Ough, M.; Lewis, A.; Bey, E. A.; Gao, J.; Ritchie, J. M.; Bornmann, W.; Boothman, D. A.; Oberley, L. W.; Cullen, J. J. Efficacy of β-lapachone in pancreatic cancer treatment: Exploiting the novel, therapeutic target NQO1. Cancer Biol. Ther. 2005, 4, 95-102.
36. Bey, E. A.; Bentle, M. S.; Reinicke, K. E.; Dong, Y.; Yang, C. R.; Girard, L.; Minna, J. D.; Bornmann, W. G.; Gao, J.; Boothman, D. A. An NQO1-and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by β-lapachone. Proc. Natl. Acad. Sci. USA 2007, 104, 11832-11837.
37. Choi, E. K.; Terai, K.; Ji, I. M.; Kook, Y. H.; Park, K. H.; Oh, E. T.; Griffin, R. J.; Lim, B. U.; Kim, J. S.; Lee, D. S.; Boothman, D. A.; Loren, M.; Song, C. W.; Park, H. J. Upregulation of NAD (P) H: Quinone oxidoreductase by radiation potentiates the effect of bioreductive β-lapachone on cancer cells. Neoplasia 2007, 8, 634-642.
38. Bentle, M. S.; Bey, E. A.; Dong, Y.; Reinicke, K. E.; Boothman, D. A. New tricks for old drugs: The anticarcinogenic potential of DNA repair inhibitors. J. Mol. Histol. 2006, 37, 203-218.
39. Li, C. J.; Li, Y. Z.; Pinto, A. V.; Pardee, A. B. Potent inhibition of tumor survival in vivo by β-lapachone plus taxol: Combining drugs imposes different artificial checkpoints. Proc. Natl. Acad. Sci. USA 1999, 96, 13369-13374.
40. Kumi-Diaka, J.; Saddler-Shawnette, S.; Aller, A.; Brown, J. Potential mechanism of phytochemical-induced apoptosis in human prostate adenocarcinoma cells: Therapeutic synergy in genistein and β-lapachone combination treatment. Cancer Cell. Int. 2004, 4, 5-14.
41. Boothman, D. A.; Pardee, A. B. Inhibition of radiation-induced neoplastic transformation by β-lapachone. Proc. Natl. Acad. Sci. USA 1989, 86, 4963-4967.
42. Li, C. J.; Averboukh, L.; Pardee, A. B. β-Lapachone, a novel DNA topoisomerase I inhibitor with a mode of action different from camptothecin. J. Biol. Chem. 1993, 268, 22463-22468.
43. Pommier, Y. Diversity of DNA topoisomerases I and inhibitors. Biochimie 1998, 80, 255-270.
44. Frydman, B.; Marton, L. J.; Sun, J. S.; Neder, K.; Witiak, D. T.; Liu, A. A.; Wang, H. M.; Mao, Y.; Wu, H. Y.; Sanders, M. M.; Liu, L. F. Induction of DNA topoisomerase II-mediated DNA cleavage by β-lapachone and related naphthoquinones. Cancer Res. 1997, 57, 620-627.
45. Neder, K.; Marton, L. J.; Liu, L. F.; Frydman, B. Reaction of β-lapachone chone and related naphthoquinones with 2-mercaptoethanol: A biomimetic model of topoisomerase II poisoning by quinones. Cell. Mol. Biol. 1998, 44, 465-474.
46. Krishnan, P.; Bastow, K. F. Novel mechanism of cellular DNA topoisomerase II inhibition by the pyranonaphthoquinone derivatives α-lapachone and β-lapachone. Cancer. Chemother. Pharmacol. 2001, 47, 187-198.
47. Pink, J. J.; Planchon, S. M.; Tagliarino, C.; Varnes, M. E.; Siegel, D.; Boothman, D. A. NAD (P) H: Quinone oxidoreductase activity is the principal determinant of β-lapachone cytotoxicity. J. Biol. Chem. 2000, 275, 5416-5424.
48. Pardee, A. B.; Li, Y. Z.; Li, C. J. Cancer therapy with beta-lapachone. Curr. Cancer Drug Targets 2002, 2, 227-242.
49. Hotez, P. J.; Molyneux, D. H.; Fenwick, A.; Kumaresan, J.; Sachs, S. E.; Sachs, J. D.; Savioli, L. Control of neglected tropical diseases. N. Engl. J. Med. 2007, 357, 1018-1027.
50. Chirac, P.; Torreele, E. Global framework on essential health R & D. Lancet, 2006, 367, 1560-1561.
51. Reddy, M.; Gill, S. S.; Kalkar, S. R.; Wu, W.; Anderson, P. J.; Rochon, P. A. Oral drug therapy for multiple neglected tropical diseases: A systematic review. JAMA 2007, 298, 1911-1924.
52. Trouiller, P.; Olliaro, P.; Torreele, E.; Orbinski, J.; Laing, R.; Ford, N. Drug development for neglected diseases: A deficient market and a public-health policy failure. Lancet 2002, 359, 2188-2194.
53. WHO. The World Health Report; World Health Organization: Geneva, Switzerland, 2002.
54. Chagas, C. Nova tripanosomíase humana. Estudos sobre a morfologia e o ciclo evolutivo de Schizotrypanum cruzi gen. nov. sp. nov., agente etiológico de nova entidade mórbida do homem. Mem. Inst. Oswaldo Cruz 1909, 1, 159-218.
55. Rocha, M. O.; Teixeira, M. M.; Ribeiro, A. L. An update on the management of Chagas cardiomyopathy. Expert Rev. Anti-Infect. Ther. 2007, 5, 727-743.
56. Brener, Z.; Andrade, Z.; Barral-Netto, M. Trypanosoma cruzi e doença de Chagas. Guanabara Koogan: Rio de Janeiro, Brazil, 1999; p. 431.
57. Dias, J. C. Globalization, inequity and Chagas disease. Cad. Saúde Pública 2007, 23 Suppl, S13-S22.
58. Carlier, Y. Congenital Chagas disease: From the laboratory to public health. Bull. Acad. R. Med. Belg. 2007, 162, 409-416.
59. Herwaldt, B. L. Laboratory-acquired parasitic infections from accidental exposures, Clin. Microbiol. Rev. 2001, 14, 659-688.
60. Atclas, J. D.; Barcan, L.; Nagel, C.; Lattes, R.; Riarte, A. Organ transplantation and Chagas disease. JAMA 2008, 299, 134-135.
61. Campos, S. V.; Strabelli, T. M.; Amato Neto, V.; Silva, C. P.; Bacal, F.; Bocchi, E. A.; Stolf, N. A. Risk factors for Chagas' disease reactivation after heart transplantation. J. Heart Lung Transplant. 2008, 27, 597-602.
62. Shikanai-Yasuda, M. A.; Marcondes C. B.; Guedes L. A.; Siqueira G. S.; Barone A. A.; Dias J. C.; Amato-Neto V.; Tolezano J. E.; Peres B. A.; Arruda Jr, E. R. Possible oral transmission of acute Chagas' disease in Brazil. Rev. Inst. Med. Trop. São Paulo 1991, 33, 351-357.
63. Steindel, M.; Kramer Pacheco, L.; Scholl, D.; Soares, M.; Moraes, M. H.; Eger, I.; Kosmann, C.; Sincero, T. C.; Stoco, P. H.; Murta, S. M.; de Carvalho-Pinto, C. J.; Grisard, E. C. Characterization of Trypanosoma cruzi isolated from humans, vectors, and animal reservoirs following an outbreak of acute human Chagas disease in Santa Catarina State, Brazil. Diagn. Microbiol. Infect. Dis. 2008, 60, 25-32.
64. Vaidian, A. K.; Weiss, L. M.; Tanowitz, H. B. Chagas' disease and AIDS. Kinetoplastid Biol. Dis. 2004, 3, 2.
65. Schmunis, G. A. Epidemiology of Chagas disease in non-endemic countries: The role of international migration. Mem. Inst. Oswaldo Cruz 2007, 102 (Suppl. 1), 75-85.
66. Moncayo, A.; Ortiz-Yanine, M. I. An update on Chagas disease (human American trypanosomiasis). Ann. Trop. Med. Parasitol. 2006, 100, 663-677.
67. Coura, J. R.; De Castro, S. L. A critical review on Chagas disease chemotherapy. Mem. Inst. Oswaldo Cruz 2002, 97, 3-24.
68. Soeiro, M. N. C.; De Castro, S. L. Trypanosoma cruzi targets for new chemotherapeutic approaches. Expert Opin. Ther. Targets 2009, 13, 105-121.
69. Croft, S. L.; Hogg, J.; Gutteridge, W. E.; Hudson, A. T.; Randall, A. W. The activity of hydroxynaphthoquinones against Leishmania donovani. J. Antimicrob. Chemother. 1992, 30, 827-832.
70. Croft, S. L.; Evans, A. T.; Neal, R. A. The activity of plumbagin and other electron carriers against Leishmania dononani and Leishmania mexicana. Ann. Trop. Med. Parasitol. 1985, 79, 651-653.
71. Hudson, A. T. Atovaquone - a novel broad-spectrum anti-infective drug. Parasitol. Today 1993, 9, 66-68.
72. Sepúlvelda-Boza, S.; Cassels, B. K. Plant metabolites active against Trypanosoma cruzi. Planta Med. 1996, 62, 98-105.
73. Docampo, R.; Cruz, F. S.; Boveris, A.; Muniz, R. P.; Esquivel, D. M. Lipid peroxidation and the generation of free radicals, superoxide anion, and hydrogen peroxide in β-lapachone-treated Trypanosoma cruzi epimastigotes. Arch. Biochem. Biophys. 1978, 186, 292-297.
74. Cruz, F. S.; Docampo, R.; Boveris, A. Generation of superoxide anion and hydrogen peroxide from β-lapachone in bacteria. Antimicrob. Agents Chemoter. 1978, 14, 630-633.
75. Boveris, A.; Docampo R.; Turrens J. F.; Stoppani, A. O. Effect of β-lapachone on superoxide anion and hydrogen peroxide production in Trypanosoma cruzi. Biochem. J. 1978, 75, 431-439.
76. Goijman, S. G.; Stoppani, A. O. Effect of sß-lapachone, a peroxide-generating quinone, on macromolecule synthesis and degradation in Trypanosoma cruzi. Arch. Biochem. Biophys. 1985, 240, 273-280.
77. Lopes, J. N.; Cruz, F. S.; Docampo, R.; Vasconcellos, M. E.; Sampaio, M. C. R.; Pinto, A. V.; Gilbert, B. In vitro and in vivo evaluation of the toxicity of 1, 4-naphtoquinone and 1, 2-naphthoquinone derivatives against Trypanosoma cruzi. Ann. Trop. Med. Parasitol. 1978, 72, 523-531.
78. Pinto, A. V.; Ferreira, V. F.; Capella, R. S.; Gilbert, B.; Pinto, M. C. F. R.; Silva, J. S. Activity of some naphthoquinones on bloodstream forms of Trypanosoma cruzi. Trans. Roy. Soc. Trop. Med. Hyg. 1987, 81, 609-610.
79. Gonçalves, A. M.; Vasconcellos, M. E.; Docampo, R.; Cruz, F. S.; De Souza, W.; Leon, W. Evaluation of the toxicity of 3-allyl-β-lapachone against Trypanosoma cruzi bloodstream forms. Mol. Biochem. Parasitol. 1980, 1, 167-176.
80. Dubin, M.; Fernandez Villamil, S. H.; Stoppani, A. O. Inhibition of microsomal lipid peroxidation and cytochrome P-450-catalyzed reactions by β-lapachone and related naphthoquinones. Biochem. Pharmacol. 1990, 39, 1151-1160.
81. De Witte, N. V.; Stoppani, A. O.; Dubin, M. 2-Phenyl-β-lapachone can affect mitochondrial function by redox cycling mediated oxidation. Arch. Biochem. Biophys. 2004, 432, 129-135.
82. Molina Portela, M. P.; Fernandez Villamil, S. H.; Perissinotti, L. J.; Stoppani, A. O. Redox cycling of o-naphthoquinones in trypanosomatids. Superoxide and hydrogen peroxide production. Biochem. Pharmacol. 1996, 52, 1875-1882.
83. Pinto, A. V.; Pinto, M. C. F. R.; Oliveira, C. G. T. Síntese das α-e β-nor-lapachonas, propriedades em meio ácido e reações com N-bromosuccinimida. An. Acad. Bras. Cien. 1982a, 54, 107-114.
84. Pinto, A. V.; Pinto, M. C. F. R.; Aguiar, M. A.; Capella, R. S. Transformações do lapachol em nafto-[1, 2-b]-furanoquinonas naturais. An. Acad. Bras. Cien. 1982b, 54, 115-118.
85. Pinto, A. V.; Ferreira, V. F.; Pinto, M. C. F. R.; Mayer, L. U. Reaction of 2-amino-1, 4-naphthoquinone derivatives with dimethyl acetylenedicarboxylate. Synth. Comm. 1985, 15, 1181-1189.
86. Lopes, C. C.; Lopes, R. S. C.; Pinto, A. V.; Costa, P. R. R. Efficient synthesis of cytotoxic quinones: 2-Acetyl-4H, 9H-naphtho[2, 3-b]furan-4, 9-dione. J. Heterocycl. Chem. 1984, 21, 621-622.
87. Chaves, J. P.; Pinto, M. C. F. R.; Pinto, A. V. Heterocyclics from quinones. I - Reaction of lapachol with primary alkyl amines. J. Braz. Chem. Soc. 1990, 1, 21-27.
88. Pinto, A. V.; Neves Pinto, C.; Pinto, M. C. F. R.; Santa Rita, R. M.; Pezzella, C.; De Castro, S. L. Trypanocidal activity of synthetic heterocyclic derivatives from active quinones from Tabebuia sp. Arzneimittelforschung 1997, 47, 74-79.
89. Neves-Pinto, C.; Dantas, A. P.; Moura, K. C. G.; Emery, F. S.; Polequevitch, P. F.; Pinto, M. C. F. R.; De Castro, S. L.; Pinto, A. V. Chemical reactivity studies with naphthoquinones from Tabebuia with anti-trypanosomal efficacy. Arzneimittelforschung 2000, 50, 1120-1128.
90. Neves-Pinto, C.; Malta, V. R.; Pinto, M. C. F. R.; Santos, R. H.; De Castro, S. L.; Pinto, A. V. A trypanocidal phenazine derived from β-lapachone. J. Med. Chem. 2002, 45, 2112-2115.
91. Moura, K. C. G.; Emery, F. S.; Neves-Pinto, C.; Pinto, M. C. F. R.; Dantas, A. P.; Salomão, K.; De Castro, S. L.; Pinto, A. V. Synthesis and trypanocidal activity of naphthoquinones isolated from Tabebuia and heterocyclic derivatives: A review from an interdisciplinary study. J. Braz. Chem. Soc. 2001, 12, 325-338.
92. De Castro, S. L.; Pinto, M. C. F. R.; Pinto, A. V. Screening of natural and synthetic drugs against Trypanosoma cruzi: Establishing a structure/activity relationship. Microbios 1994, 78, 83-90.
93. Moura, K. C. G.; Salomão, K.; Menna-Barreto, R. F. S.; Emery, F. S.; Pinto, M. C. F. R.; Pinto, A. V.;
94. De Castro, S. L. Studies on the trypanocidal activity of semi-synthetic pyran[b-4, 3]naphtho[1, 2-d]imidazoles from β-lapachone. Eur. J. Med. Chem. 2004, 39, 639-645.
95. Pinto, A. V.; Menna-Barreto, R. F. S.; De Castro, S. L. Naphthoquinones Isolated from Tabebuia: A Review About the Synthesis of Heterocyclic Derivatives, Screeening against Trypanosoma cruzi and Correlation Structure-trypanocidal Activity. In Recent Progress in Medicinal Plants; Govil, J. N., Ed.; Phytomedicines Studium Press: Houston, TX, USA, 2006; Vol. 16, pp. 112-127.
96. Menna-Barreto, R. F. S.; Henriques-Pons, A.; Pinto, A. V.; Morgado-Diaz, J. A.; Soares, M. J.; De Castro, S. L. Effect of a β-lapachone-derived naphthoimidazole on Trypanosoma cruzi: Identification of target organelles. J. Antimicrob. Chemother. 2005, 56, 1035-1041.
97. Menna-Barreto, R. F. S.; Corrêa, J. R.; Pinto, A. V.; Soares, M. J.; De Castro, S. L. Mitochondrial disruption and DNA fragmentation in Trypanosoma cruzi induced by naphthoimidazoles synthesized from β-lapachone. Parasitol. Res. 2007, 101, 895-905.
98. Menna-Barreto, R. F. S.; Corrêa, J. R.; Cascabulho, C. M.; Fernandes, M. C.; Pinto, A. V.; Soares, M. J.; De Castro, S. L. Naphthoimidazoles promote different death phenotypes in Trypanosoma cruzi. Parasitology 2009a, 136, 499-510.
99. Menna-Barreto, R. F. S.; Salomão, K.; Dantas, A. P.; Santa-Rita, R. M.; Soares, M. J.; Barbosa, H. S.; De Castro, S. L. Different cell death pathways induced by drugs in Trypanosoma cruzi: An ultrastructural study. Micron 2009b, 40, 157-168.
100. Winkelmann, E.; Raether, W.; Sinharay, A. Chemotherapeutically active nitro compounds. 4, 5-Nitroimidazoles (Part II). Arzneimittelforschung 1978, 28, 351-366.
101. McCabe, R. E.; Araújo, F. G.; Remington, J. S. Ketoconazole protects against infection with Trypanosoma cruzi in a murine model. Am. J. Trop. Med. Hyg. 1983, 32, 960-962.
102. Chabala, J. C.; WQaits, V. B.; Ikeler, T.; Patchett, A. A.; Payne, L.; Peterson, L. H.; Reamer, R. A.; Hoogsteen, K.; Wyvratt, M.; Hanson, W. L.; Fisher, M. H. 1-(Substituted) benzyl-5-aminiimidazole-4-carboxamides are potent orally active inhibitors of Trypanosoma cruzi in mice. Experientia 1991, 47, 51-53.
103. Nothemberg, M. S.; Takeda, G. K. F.; Najjar, R. Adducts of nitroimidazole derivatives with Rhodium (II) carboxylates: Synthesis, characterization and evaluation of antichagasic activities. J. Inorg. Biochem. 1991, 42, 217-229.
104. Amuchastegui, P. I.; Moretti, E. R.; Basso, B.; Sperandeo, N.; de Bertorello, M. M. Isoxazolylnaphthoquinone effects on the growth of Trypanosoma cruzi. Rev. Argent. Microbiol. 1990, 22, 199-207.
105. Tarlovsky, M. N.; Goijman, S. G.; Molina Portela, M. P.; Stoppani, A. O. Effects of isoxazolylnaphthoquinoneimines on growth and oxygen radical production in Trypanosoma cruzi and Crithidia fasciculata. Experientia 1990, 46, 502-505.
106. Sperandeo, N. R.; Brun, R. Synthesis and biological evaluation of pyrazolylnaphthoquinones as new potential antiprotozoal and cytotoxic agents. Chem. Bio. Chem. 2003, 4, 69-72.
107. Sperandeo, N. R.; Brinon, M. C.; Brun, R. Synthesis, antiprotozoal and cytotoxic activities of new N-(3, 4-dimethyl-5-isoxazolyl)-1, 2-naphthoquinone-4-amino derivatives. Farmaco 2004, 59, 431-435.
108. Fournet, A.; Angelo, A.; Munoz, V.; Roblot, F.; Hocquemiller, R.; Cava, A. Biological and chemical studies of Pera benensis, a Bolivian plant used in folk medicine as a treatment of cutaneous leishmaniasis. J. Ethnopharmacol. 1992, 37, 159-164.
109. Rojas de Arias, A.; Inchausti, A.; Ascurrat, M.; Freitas, N.; Rodriguez, E.; Fournet, A. In vitro activity and mutagenicity of bisbenzylisolquinolines and quinones against Trypansoma cruzi trypomastigotes. Phytother. Res. 1994, 8, 141-144.
110. Hazra, B.; Sur, P.; Sur, B.; Banerjee, A.; Roy, D. K. Studies on the biological activity of of diospyrin towards Ehrlich ascites carcinoma in Swiss A mice. Planta Med. 1984, 58, 295-298.
111. Yardley, V.; Snowdown, D.; Croft, S. L.; Hazra, B. In vitro activity of diospyrin and derivatives against Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei brucei. Phytother. Res. 1996, 10, 559-562.
112. Ribeiro-Rodrigues, R.; Dos Santos, W.; Oliveira, A. B.; Snieckus, V.; Zani, C. L.; Romanha, A. J. Growth inhibitory effect of naphthofuran and naphthofuranquinone derivatives on Trypanosoma cruzi epimastigotes. Bioorg. Med. Chem. 1995, 5, 1509-1512.
113. Krauth-Siegel, R. L.; Comini, M. A. Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochim. Biophys. Acta. 2008, 1780, 1236-1248.
114. Henderson, G. B.; Ulrich, P.; Fairlamb, A. H.; Rosenberg, J.; Pereira, M.; Sela, M.; Cerami, A. "Subversive" substrates for the enzyme trypanothione disulfide reductase: Alternative approach to chemotherapy of Chagas disease. Proc. Natl. Acad. Sci. USA 1988, 85, 5374-5378.
115. Jockers-Scherübl, M. C.; Schirmer, R. H.; Krauth-Siegel, R. L. Trypanothione reductase from Trypanosoma cruzi. Catalytic properties of the enzyme and inhibition studies with trypanocidal compounds. Eur. J. Biochem. 1989, 180, 267-272.
116. Salmon-Chemin, L.; Lemaire, A.; De Freitas, S.; Deprez, B.; Sergheraert, C.; Davioud-Charvet, E. Parallel synthesis of a library of 1, 4-naphthoquinones and automated screening of potential inhibitors of trypanothione reductase from Trypanosoma cruzi. Bioorg. Med. Chem. Lett. 2000, 10, 631-635.
117. Salmon-Chemin, L.; Buisine, E.; Yardley, V.; Kohler, S.; Debreu, M. A.; Landry, V.; Sergheraert, C.; Croft, S. L.; Krauth-Siegel, R. L.; Davioud-Charvet, E. 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. 2001, 44, 548-565.
118. Zani, C. L.; Chiari, E.; Krettli, A. U.; Murta, S. M.; Cunningham, M. L.; Fairlamb, A. H.; Romanha, A. J. Anti-plasmodial and anti-trypanosomal activity of synthetic naphtho[2, 3-b]thiopen-4, 9-quinones. Bioorg. Med. Chem. 1997, 5, 2185-2192.
119. Zani, C. L.; Fairlamb, A. H. 8-Methoxy-naphtho[2, 3-b]thiophen-4, 9-quinone, a non-competitive inhibitor of trypanothione reductase. Mem. Inst. Oswaldo Cruz 2003, 98, 565-568.
120. Tapia, R. A.; Salas, C.; Morello, A.; Maya, J. D.; Toro-Labbe, A. Synthesis of dihydronaphthofurandiones and dihydrofuroquinolinediones with trypanocidal activity and analysis of their stereoelectronic properties. Bioorg. Med. Chem. 2004, 12, 2451-2458.
121. Salas, C.; Tapia, R. A.; Ciudad, K.; Armstrong, V.; Orellana, M.; Kemmerling, U.; Ferreira, J.; Maya, J. D.; Morello, A. Trypanosoma cruzi: Activities of lapachol and α-and β-lapachone derivatives against epimastigote and trypomastigote forms. Bioorg. Med. Chem. 2008, 16, 668-674.
122. Goulart, M. O.; Falkowski, P.; Ossowski, T.; Liwo, A. Electrochemical study of oxygen interaction with lapachol and its radical anions. Bioelectrochemistry 2003, 59, 85-87.
123. Silva Júnior, E. N.; Menna-Barreto, R. F. S.; Pinto, M. C. F. R.; Silva, R. S. F.; Teixeira, D. V.; Souza, M. C. B. V.; de Simone, C. A.; De Castro, S. L.; Ferreira, V. F.; Pinto, A. V. Naphthoquinoidal [1, 2, 3]-triazole, a new structural moiety active against Trypanosoma cruzi. Eur. J. Med. Chem. 2008a, 43, 1774-1780.
124. Silva Júnior, E. N.; Souza, M. C. B. V.; Fernandes, M. C.; Menna-Barreto, R. F. S.; Pinto, M. C. F. R.; Lopes, F. A.; de Simone, C. A.; Andrade, C. K.; Pinto, A. V.; Ferreira, V. F.; De Castro, S. L. Synthesis and anti-Trypanosoma cruzi activity of derivatives from nor-lapachones and lapachones. Bioorganic. Med. Lett. 2008b, 16, 5030-5038.
125. Silva, R. S. F.; Costa, E. M.; Trindade, U. L. T.; Teixeira, D. V.; Pinto, M. C. F. R.; Santos, G. L.; Malta, V. R. S.; De Simone, C. A.; Pinto, A. V.; De Castro, S. L. Synthesis of naphthofuranquinones with activity against Trypanosoma cruzi. Eur. J. Med. Chem. 2006, 41, 526-530.
126. Menna-Barreto, R. F. S.; Gonçalves, R. L. S.; Costa, E. M.; Silva, R. S. F.; Pinto, A. V.; Oliveira, M. F.; De Castro, S. L. The activity on Trypanosoma cruzi of novel synthetic naphthoquinones is mediated by mitochondrial dysfunction. Free Rad. Biol. M Ed. 2009c, in press. © 2009