Chagas disease is an infectious illness with a broad distribution throughout the South American and African continents, importantly influencing human morbidity and mortality and a controversial relationship with the onset of cancers, especially of the gastrointestinal tract system. In addition, it is listed by the World Health Organization (WHO) as one ofthe most neglected tropical diseases. Although Chagas disease (CD) was discovered more than 100 years ago, the existing therapies show low efficacy and serious side effects and developing safer and more effective drugs remains a hard challenge. Thus, this review highlights the main, novel and promising treatments against Trypanosoma cruzi, including biomacromolecules, natural products, vaccines, and metabolic pathway targets and highlights a worsening of esophageal cancer prognosis in chagasic patients. Moreover, we also discuss the perspectives of obtaining original optimized drugs that take advantage of organic and inorganic medicinal chemistry advances, as well as molecular modeling and biotechnology.
| Published in |
Cancer Research Journal (Volume 2, Issue 6-1)
This article belongs to the Special Issue Lifestyle and Cancer Risk |
| DOI | 10.11648/j.crj.s.2014020601.12 |
| Page(s) | 11-29 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2014. Published by Science Publishing Group |
Chagas, Cancer, Drug, Neglected Disease, Trypanosoma cruzi
| [1] | Hotez P J, et al. (2007) Control of neglected tropical diseases. N Engl J Med 357, 1018 - 27. |
| [2] | WHO (World Health Organization). (2002) Expert Committee on the Control of Chagas Disease. Control of Chagas disease: second report of the WHO expert committee. Geneva. 1 - 109. |
| [3] | Muratore C A, Baranchuk A. (2010) Current and emerging therapeutic options for the treatment of chronic chagasic cardiomyopathy. Vasc Health Risk Manag 6, 593 – 601. |
| [4] | Neres J, et al. (2009) Discovery of novel inhibitors of Trypanosoma cruzi trans-sialidase from in silico screening. Bioorg Med Chem Letters 19 (3), 589 - 96. |
| [5] | Schmunis G A, Yadon Z E (2010) Chagas disease: A Latin American health problem becoming a world health problem. Acta Trop 115 (1-2), 14 – 21. |
| [6] | Pozas R, Carballo J, Castro C, Rubio J. (2005) Synthesis and in vitro antitrypanosomal activity of novel nifurtimox analogues. Bioorg Med Chem Letters 15 (5), 1417 - 21. |
| [7] | Schofield C J, Dias J C P. (1991) A cost-benefit analysis of Chagas disease control. Mem Inst Oswaldo Cruz 86 (3), 285 – 95. |
| [8] | Rosenbaum M B (1964) Chagasic myocardiopathy. Prog Cardiovasc Dis 7, 199 – 225. |
| [9] | Chapadeiro E, Lopes E R, Mesquita P M, Pereira F E L. (1964) Incidências de mega associadas à cardiopatia chagásica. Rev Inst Med Trop 6, 287 - 91. |
| [10] | Alviano D S, et al. (2007) Conventional therapy and promising plant-derived compounds against trypanosomatid parasites. Front Microbiol 3, 283. |
| [11] | El-Sayed N M, et al. (2005) The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 309 (5733), 409 – 15. |
| [12] | Silva A L M, et al. (2007) Desenvolvimento de método analítico por CLAE em comprimidos de benznidazol para a doença de chagas. Quim Nova 30 (5), 1163 - 6. |
| [13] | Coura J R, Borges-Pereira J. (2010) Chagas disease: 100 years after its discovery. A systemic review. Acta Trop 115 (1-2), 5 – 13. |
| [14] | Lustig E S, et al. (1980) Association of Chagas disease and cancer. Medicina (B Aires) 40, 43 - 6. |
| [15] | Dominical V M, et al. (2010) Chagas disease and gynecologic neoplasias. Ann Diagn Pathol 14 (5), 337 – 40. |
| [16] | Granger D N, Senchenkova E S R Inflammation and the Microcirculation. Angiogenesis. Morgan & Claypool Life Sciences; 2010, Chapter 6 |
| [17] | Jr A R, Rassi A, Rezende J M (2012) American Trypanosomiasis (Chagas Disease). Infect Dis Clin N Am 26 (2), 275 – 91. |
| [18] | Jr A R, Rassi A, Marin-Neto J A. (2010) Chagas disease. Lancet 375 (9723), 1388 – 402. |
| [19] | Rassi A, et al. Clinical phases and forms of Chagas disease. In: Telleria J, Tibayrenc M, editors. American trypanosomiasis (Chagas disease). One hundred years of research. 1st edition. Burlington (MA): Elsevier Inc; 2010, p. 709–41. |
| [20] | Meneses A C, et al. (1989) Megas and cancer. Cancer of the large intestine in chagasic patients with megacolon. Arq Gastroenterol. 26 (1-2), 13 - 6. |
| [21] | Joly E, Hudrisier D. (2003) What is trogocytosis and what is its purpose? Nat Immunol 4 (9), 815. |
| [22] | Vanherberghen B, et al. (2004) Human and murine inhibitory natural killer cell receptors transfer from natural killer cells to target cells. Proc Natl Acad Sci USA 101(48), 16873 - 8. |
| [23] | Mukherjee S, et al., (2014) Trypanosoma cruzi invasion is associated with trogocytosis. Microb Infect 1-19. |
| [24] | Ralston K S, Solga M D, Mackey-Lawrence N M, Bhattacharya S, Petri Jr WA. (2014) Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion. Nature 508, 526 - 30. |
| [25] | Kim J O, et al. (2007) Inhibition of Lewis lung carcinoma growth by Toxoplasma gondii through induction of Th1 immune responses and inhibition of angiogenesis. J Korean Med Sci 22, S38 – S46. |
| [26] | Michalak M, Robert Parker J M, Opas M (2002) Ca2+ signaling and calcium binding chaperones of the endoplasmic reticulum. Cell Calcium 32 (5–6), 269 – 78. |
| [27] | Rojiani M V, Finlay B B, Gray V, Dedhar S. (1991) In vitro interaction of a polypeptide homologous to human Ro/SS-A antigen (calreticulin) with a highly conserved amino acid sequence in the cytoplasmic domain of integrin alpha subunits. Biochem 30 (41), 9859 – 66. |
| [28] | Burns K, et al. (1994) Modulation of gene expression by calreticulin binding to the glucocorticoid receptor. Nature 367 (6462), 476 – 80. |
| [29] | Ramírez G, et al. (2012) Roles of Trypanosoma cruzi calreticulin in parasite–host interactions and in tumor growth. Mol Immunol. 52 (3-4), 133 - 40. |
| [30] | Mayer M, Rocha H L. (1912) Zur Entwicklung von Schizotrypanum cruzi in Saengatieren. Archiv fur schisffs- und Tropen-Hygiene 16, 90 - 94. |
| [31] | Bock M, Haberkorn A, Herlinger H, Mayer K H, Petersen S. (1972) The struture activity relationship of 4-5’-nitrofufurylidene-amino-tetrahydro-4H-1,4-thiazine-1,1-dioxides active against Trypanosoma cruzi. Arzneim-Forsh. 22, 1564 - 9. |
| [32] | Urbina J A. (2009) Ergosterol biosynthesis and drug development for chagas disease. Mem Inst Oswaldo Cruz 104 (1), 311 - 318. |
| [33] | Docampo R, Mason R P, Mottley C, Muniz R P. (1981). Generation of free radicals induced by nifurtimox in mammalian tissues. J Biol Chem 256 (21), 10930 - 3. |
| [34] | Docampo R. (1990) Sensitivity of parasites to free radical damage by antiparasitic drugs. Chem Biol Interact 73, 1-27. |
| [35] | Viodé C, et al. J. (1999) Enzymatic reduction studies of nitroheterocycles. Biochem Pharmacol 57 (5), 549 - 57. |
| [36] | Hall B S, Bot C, Wilkinson S R. (2011) Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites. J Biol Chem 286 (15), 13088 - 95. |
| [37] | Blumenstiel K, Schöneck R, Yardley V, Croft S L, Krauth-Siegel R L. (1999) Nitrofuran drugs as common subversive substrates of Trypanosoma cruzi lipoamide dehydrogenase and trypanothione reductase. Biochem Pharmacol 58 (11), 1791 - 9. |
| [38] | Wilkinson S R, Kelly J M. (2009) Trypanocidal drugs: mechanisms, resistance and new targets. Expert Rev Mol Med 11, e31. |
| [39] | Roldán M D, Pérez-Reinado E, Castillo F, Moreno-Vivián C. (2008) Reduction of polynitroaromatic compounds: the bacterial nitroreductases. FEMS Microbiol Rev 32 (3), 474 - 500. |
| [40] | Streeter A J, Hoener B A. (1988) Evidence for the involvement of a nitrenium ion in the covalent binding of nitrofurazone to DNA. Pharm Res 5 (7), 434 - 6. |
| [41] | Kubata B K., et al. (2002) A key role for old yellow enzyme in the metabolism of drugs by Trypanosoma cruzi. J Exp Med 196 (9), 1241 - 51. |
| [42] | Wilkinson S R, Taylor M C, Horn D, Kelly J M, Cheeseman I. (2008). A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes. Proc Natl Acad Sci USA 105 (13), 5022 - 7. |
| [43] | Cançado J R. (2002) Long term evaluation of etiological treatment of chagas disease with benznidazole. Rev Inst Med Trop 44 (1), 29 - 37. |
| [44] | Urbina J A, Docampo R. (2003) Specific chemotherapy of chagas disease: controversies and advances. Trends Parasitol 19 (11), 495 - 501. |
| [45] | Altcheh J, Moscatelli G, Moroni S, Garcia-Bournissen F, Freilij H. (2011) Adverse events after the use of benznidazole in infants and children with Chagas disease. Pediatrics.127 (1), e212 - 8. |
| [46] | Soeiro M N C, De Castro S L. (2009) Trypanosoma cruzi targets for new chemotherapeutic approaches. Exp Opin Ther Targets 13 (1), 105 - 21. |
| [47] | Buckner F S, Navabi N. (2010) Advances in Chagas disease drug development: 2009-2010. Curr Opin Infect Dis 23 (6), 609 - 16. |
| [48] | Romanha, A.J., et al. (2010). In vitro and in vivo experimental models for drug screening and development for Chagas disease. Mem Inst Oswaldo Cruz 105 (2), 233 - 8. |
| [49] | Dias L C, et al. (2009) Quimioterapia da doença de Chagas: estado da arte e perspectivas no desenvolvimento de novos fármacos. Quim Nova 32 (9), 2444 - 57. |
| [50] | Corsini A, Bellosta S, Baetta R. (1999) New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther 84 (3), 413 - 428. |
| [51] | Itsvan E S, Deisenhofer J. (2001) Structural Mechanism for Statin Inhibition of HMG-CoA Reductase. Science 292 (5519), 1160 - 4. |
| [52] | Yasmin S, et al. (2012) Mevalonate governs interdependency of ergosterol and siderophore biosyntheses in the fungal pathogen Aspergillus fumigatus. Proc Natl Acad Sci USA 109 (8), E497 - 504. |
| [53] | Hankins E G, Gillespie J R, Aikenhead K, Buckner F S. (2005) Upregulation of sterol C14-demethylase expression in Trypanosoma cruzi treated with sterol biosynthesis inhibitors. Mol Biochem Parasitol 144 (1), 68 - 75. |
| [54] | Urbina J A, et al. (1993) Mevinolin (lovastatin) potentiates the antiproliferative effects of ketoconazole and terbinafine against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies. Antimicrob Agents Chemother 37 (3), 580 – 91. |
| [55] | Shanes J G, Minadeo K N, Moret A, Groner M, Tabaic S A. (2007) Statin therapy in heart failure: prognostic effects and potential mechanisms. Am Heart J 154 (4), 617 – 23. |
| [56] | Weis M, Heeschen C, Glassford A J, Cooke J P. (2002) Statins have biphasic effects on angiogenesis. Circulation. 105 (6), 739 – 45. |
| [57] | Feldman A M, McNemara D. (2000). Medical Progress: Myocarditis. N Engl J Med 343, 1388 – 98. |
| [58] | Melo L, et al. (2011) Low doses of simvastatin therapy ameliorate cardiac inflammatory remodeling in Trypanosoma cruzi-infected dogs. Am J Trop Med Hyg 84 (2), 325 - 31. |
| [59] | Cheng X, et al. (2005) Effects of Atorvastatin on Th polarization in patients with acute myocardial infarction. Eur J Heart Fail 7 (7), 1099 – 104. |
| [60] | Robinson J G. (2008) Models for describing relations among the various statin drugs, low-density lipoprotein cholesterol lowering, pleiotropic effects and cardiovascular risk. Am J Cardiol 101 (7), 1009 – 15. |
| [61] | Montalvetti A, et al. (2003) Farnesyl pyrophosphate synthase is an essential enzyme in Trypanosoma brucei. J Biol Chem 278 (19), 17075 – 83. |
| [62] | Sigman L, Sánchez V M, Turjanski A G. (2006) Characterization of the farnesyl pyrophosphate synthase of Trypanosoma cruzi by homology modeling and molecular dynamics. J Mol Graphics Mod 25 (3), 245 – 52. |
| [63] | Montalvetti A, et al. (2001) Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase. J Biol Chem 276 (36), 33930-7. |
| [64] | Szajnman S H, Montalvetti A, Wang Y, Docampo R, Rodriguez J B. (2003) Bisphosphonates derived from fatty acids are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase. Bioorg Med Chem Lett 13 (19), 3231 - 5. |
| [65] | Szajnman S H, Ravaschino E L, Docampo R, Rodriguez J B. (2005) Synthesis and biological evaluation of 1-amino-1,1-bisphosphonates derived from fatty acids against Trypanosoma cruzi targeting farnesyl pyrophosphate synthase. Bioorg Med Chem Lett 15 (21), 4685 - 90. |
| [66] | Martin B M, et al. (2001) Bisphosphonates Inhibit the Growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: A Potential Route to Chemotherapy. J Biol Chem 44 (6), 909 – 16. |
| [67] | Garzoni L R, et al. (2004) Antiparasitic activity of risedronate in a murine model of acute Chagas’ disease. Int J Antimicrob Agents 23 (3), 286 - 90. |
| [68] | Esteva M I, et al. (2005) Benzophenone-based farnesyltransferase inhibitors with high activity against Trypanosoma cruzi. J Med Chem 48 (23), 7186 - 91. |
| [69] | Bouzahzah B, Jelicks L A, Morris S A, Weiss L M, Tanowitz H B. (2005) Risedronate in the treatment of Murine Chagas' disease. Parasitol Res 96 (3), 184 - 7. |
| [70] | Demoro B, et al. (2010) Risedronate metal complexes potentially active against Chagas disease. J Inorg Biochem 104 (12), 1252 – 1254. |
| [71] | Pandit J, et al. (2000) Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis. J Biol Chem 275 (39), 30610 - 7. |
| [72] | Urbina J A, et al. (2004) In vitro and in vivo activities of E5700 and ER-119884, two novel orally active squalene synthase inhibitors, against Trypanosoma cruzi. Agents Chemother 48 (7), 2379 - 87. |
| [73] | Linares G G., et al. (2007) Fluorine-containing aryloxyethyl thiocyanate derivatives are potent inhibitors of Trypanosoma cruzi and Toxoplasma gondii proliferation. Bioorg. Med Chem Letters 17 (18), 5068 - 71. |
| [74] | Urbina J A, et al. (2003) Parasitological cure of acute and chronic experimental Chagas disease using the long- acting experimental triazole TAK-187.Activity against drug-resistant Trypanosoma cruzi strains. Int J Antimicrob Agents 21 (1), 39 - 48. |
| [75] | Szajnman S H, et al. (2000) Design and synthesis of aryloxyethyl thiocyanate derivatives as potent inhibitors of Trypanosoma cruzi proliferation. J Med Chem 43 (9), 1826 – 40. |
| [76] | Elhalem E, et al. (2002) Design, synthesis and biological evaluation of aryloxyethyl thiocyanate derivatives against Trypanosome cruzi. J Med Chem 45, 3984 – 99. |
| [77] | Pandit J, et al. (2000) Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis. J Biol Chem 275 (39), 30610 - 7. |
| [78] | Oldfield E. (2010) Targeting isoprenoid biosynthesis for drug discovery: bench to bedside. Acc Chem Res 43 (9), 1216 - 26. |
| [79] | Sealey-Cardona M, et al. (2007) Kinetic characterization of squalene synthase from Trypanosoma cruzi: selective inhibition by quinuclidine derivatives. Antimicrob Agents Chemother 51 (6), 2123 - 9. |
| [80] | Orenes S L, et al. (2005) Biphenylquinuclidines as inhibitors of squalene synthase and growth of parasitic protozoa. Bioorg Med Chem 13 (10), 3519 - 29. |
| [81] | Buckner F S, Griffin J H, Wilson A J, Van Voorhis W C. (2001) Potent anti-Trypanosoma cruzi activities of oxidosqualene cyclase inhibitors. Antimicrob. Agents Chemother. 45 (4), 1210 - 5. |
| [82] | Oliaro-Bosso S, et al. (2005) Analogs of squalene and oxidosqualene inhibit oxidosqualene cyclase of Trypanosoma cruzi expressed in Saccharomyces cerevisiae. Lipids 40 (12), 1257 - 62. |
| [83] | Dehmlow H, et al. (2003) Synthesis and structure-activity studies of novel orally active non-terpenoic 2,3-oxidosqualene cyclase inhibitors. J Med Chem 46 (15), 3354 - 70. |
| [84] | Balliano G., et al. (2009) Oxidosqualene cyclase from Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii and Arabidopsis thaliana expressed in yeast: A model for the development of novel antiparasitic agents. Bioorg Med Chem Lett 19 (3), 718 – 23. |
| [85] | Thoma R, et al. (2004) Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase. Nature 432 (7013), 118 - 22. |
| [86] | Urbina J A, Payares G, Sanoja C, Lira R, Romanha A J. (2003) In vitro and vivo activities of ravuconazole on Trypanosoma cruzi, the causative agent of Chagas diseases. Int J Antimicrob Agents 21 (1), 27 - 38. |
| [87] | De Castro S L. (1993) The challenge of Chagas disease chemotherapy: an update of drugs assayed against Trypanosoma cruzi. Acta Trop 53 (2), 83 - 98. |
| [88] | Santa-Rita M R, Lira R, Barbosa H S, Urbina J A, De Castro S L. (2005) Anti-proliferative synergy of lysophospholipid analogues and ketoconazole against Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae): cellular and ultrastructural analysis. J Antim Chemother 55 (5), 780 - 4. |
| [89] | Buckner F S, Wilson A J, White T C, Van Voorhis W C. (1998) Induction of resistance to azole drugs in Trypanosoma cruzi. Antimicrob. Agents Chemother. 42 (12), 3245 - 50. |
| [90] | Chen C K, et al. (2009) Trypanosoma cruzi CYP51 Inhibitor Derived from a Mycobacterium tuberculosis Screen Hit. PLoS Negl Trop Dis 3 (2), e372. |
| [91] | Molina J, Brener Z, Romanha A J, Urbina J A. (2000) In vivo activity of the bis-triazole D0870 against drug-susceptible and drug-resistant strains of the protozoan parasite Trypanosoma cruzi. J Antim Chemother 46 (1), 137 - 40. |
| [92] | Silva D T, De Nazareth S L M, Meirelles M, Almeida D, Urbina J A, Pereira M C. (2006) Cytoskeleton reassembly in cardiomyocytes infected by Trypanosoma cruzi is triggered by treatment with ergosterol biosynthesis inhibitors. Int J Antimicrob Agents 27 (6), 530 - 7. |
| [93] | Ferraz M L, Gazzinelli R T, Alves R O, Urbina J A, Romanha A J. (2007) The Anti-Trypanosoma cruzi activity of posaconazole in a murine model of acute Chagas' disease is less dependent on gamma interferon than that of benznidazole. Antimicrob Agents Chemother 51(4), 1359-64. |
| [94] | Suryadevara K P, et al. (2009) Structurally simple inhibitors of lanosterol 14α-demethylase are efficacious in a rodent model of acute Chagas disease. J Med Chem 52 (12), 3703 – 15. |
| [95] | Olivieri B P, et al. (2010) A comparative study of posaconazole and benznidazole in the prevention of heart damage and promotion of trypanocidal immune response in a murine model of Chagas disease. Int J Antimicrob Agents 36 (1), 79 - 83. |
| [96] | Veiga-Santos, P, et al. (2012) Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi. Int J Antimicrob Agents 40 (1), 61 - 71 |
| [97] | Urbina J A, Concepcion L J, Montalvetti A, Rodriguez B J, Docampo R. (2003) Mechanism of action of 4-phenoxyphenoxyethyl thiocyanate (WC-9) against Trypanosoma cruzi, the causative agent of Chagas’ disease. Antimicrob Agents Chemother 47 (6), 2047 – 50. |
| [98] | Diniz L F, et al. (2010) Effects of Ravuconazole Treatment on Parasite Load and Immune Response in Dogs Experimentally Infected with Trypanosoma cruzi. Antimicrob Agents Chemother 54 (7), 2979 - 86. |
| [99] | Molina J, et al. (2001) Cure of experimental Chagas’ disease by the bis-triazole DO870 incorporated into ‘stealth’ polyethyleneglycol-polylactide nanospheres. J Antim Chemother 47 (1), 101 - 4. |
| [100] | Urbina J A, Lira R, Visbal G, Bartroli J. (2000) In vitro antiproliferative effects and mechanism of action of the newtriazole derivative UR-9825 against the protozoan parasite Trypanosoma (Schizotrypanum) cruzi. Antimicrob Agents Chemother 44 (9), 2498 - 2502. |
| [101] | Uehara L A, et al. (2012) Cruzipain promotes Trypanosoma cruzi adhesion to Rhodnius prolixus Midgut. PLoS Negl Trop Dis 6 (12), e1958. |
| [102] | Scharfstein J, et al. (2000) Host cell invasion by Trypanosoma cruzi is potentiated by activation of bradykinin B(2) receptors. J Exp Med 192 (9), 1289 - 1300. |
| [103] | Aparicio I M, Scharfstein J, Lima A P. (2004). A new cruzipain-mediated pathway of human cell invasion by Trypanosoma cruzi requires trypomastigote membranes. Infect Immun 72 (10), 5892 - 902. |
| [104] | Andrade D, et al. (2012) Trypanosoma cruzi Trypanosoma cruzi invades host cells through the activation of endothelin and bradykinin receptors: a converging pathway leading to chagasic vasculopathy. Br J Pharmacol 165 (5), 1333 - 47. |
| [105] | Berasain P, Carmona C, Frangione B, Cazzulo J J, Goñi F. (2003) Specific cleavage sites on human IgG subclasses by cruzipain, the major cysteine proteinase from Trypanosoma cruzi. Mol Biochem Parasitol 130 (1), 23 - 9. |
| [106] | Engel J C, Doyle P S, Palmer J, Bainton D F, McKerrow J H. (1998) Cysteine protease inhibitors after Golgi complex ultra structure and function in Trypanosoma cruzi. J Cell Science 111 (5), 597 - 606. |
| [107] | Doyle S P, Zhou M Y, Engel C J, McKerrow H J. (2007) A cysteine protease inhibitor cures Chagas’ disease in an immunodeficient-mouse model of infection.Antimicrob. Agents Chemother 51 (11), 3932 – 9. |
| [108] | Yong V, et al. (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 (1), 47 - 59. |
| [109] | Reis F C, et al. (2007) The propeptide of cruzipain--a potent selective inhibitor of the trypanosomal enzymes cruzipain and brucipain, and of the human enzyme cathepsin. F FEBS J 274 (5), 1224 - 34. |
| [110] | Chen Y T, et al. (2010) In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi. PLoS Negl Trop Dis 4 (9), e825. |
| [111] | Flohé L. (2012) The trypanothione system and its implications in the therapy of trypanosomatid diseases. Int J Med Microbiol 302 (4-5), 216 - 20. |
| [112] | Graebin C S, et al. (2009) Antiprotozoal agents: an overview. Anti-Infective agents Med Chem 8, 345-366. |
| [113] | Lo Presti M S, et al. (2004) Thioridazine treatment prevents cardiopathy in Trypanosoma cruzi infected mice. Int J Antimicrob Agents 23 (6), 634 - 6. |
| [114] | Salmon-Chemin L, et al. (2001) 2- and 3-substituted 1,4-naphtoquinone 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 (4), 548 - 65. |
| [115] | Wenck M A, Medrano F J, Eakin A E, Craig S P. (2004) Steady-state kinetics of the hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi. Biochem Biophys Acta 1700 (1), 11 - 8. |
| [116] | Canyuk B, Medrano F J, Wenck M A, Focia P J, Eakin A E, Craig S P 3rd. (2004) Interactions at the dimer interface influence the relative efficiencies for purine nucleotide synthesis and pyrophosphorolysis in a phosphoribosyltransferase. J Mol Biol 335 (4), 905 - 21. |
| [117] | Ullman B, Carter D. (1997) Molecular and biochemical studies on the hypoxanthine-guanine phosphoribosyltransferases of the pathogenic haemoflagellates. Int J Parasitol 27 (2), 203 - 13. |
| [118] | Focia P J, Craig III S P, Eakin A E. (1998) Approaching the transition state in the crystal structure of a phosphoribosyltransferase. Biochem 37 (49), 17120 - 7. |
| [119] | Freymann D M, et al. (2000) Efficient identification of inhibitors targeting the closed active site conformation of HPRT from Trypanosoma cruzi. Chem Biol 7 (12), 957 - 68. |
| [120] | Lauria-Pires L, Castro C N, Emanuel A, Prata A. (1998) Ineficácia do allopurinol em pacientes na fase aguda da doença de Chagas. Rev Soc Med Trop 21 (2), 79 - 80. |
| [121] | Héroux A, White E L, Ross L J, Borhani D W. (1999) Crystal structures of the Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase-GMP and -IMP complexes: comparison of purine binding interactions with the XMP complex. Biochemistry 38 (44), 14485 - 94. |
| [122] | Cortés F, Pastor N, Mateos S, Domínguez I. (2003) Roles of DNA topoisomerases in chromosome segregation and mitosis. Mutat Res 543 (1), 59 - 66. |
| [123] | Zuma A A, Cavalcanti D P, Maia M C P, De Souza W, Mottaa M C M. (2011) Effect of topoisomerase inhibitors and DNA-binding drugs on the cell proliferation and ultrastructure of Trypanosoma cruzi. Int J Antimicrob Agents 37 (5), 449 – 56. |
| [124] | Ray S, Hazra B, Mittra B, Das A, Majumder H K. (1998) Diospyrin, a bisnaphthoquinone: a novel inhibitor of type I DNA topoisomerase of Leishmania donovani. Mol Pharmacol 54 (6), 994 – 9. |
| [125] | Teicher B A. (2008) Next generation topoisomerase I inhibitors: rationale and biomarker strategies. Biochem.Pharmacol. 75 (6), 1262 – 71. |
| [126] | Palchaudhuri R, Hergenrother P J. (2007) DNA as a target for anticancer compounds: methods to determine the mode of binding and the mechanism of action. Curr Opin Biotechnol 18 (6), 497 – 503. |
| [127] | Bodley A L, Shapiro T A. (1995) Molecular and cytotoxic effects of camptothecin, a topoisomerase I inhibitor, on trypanosomes and Leishmania. Proc Natl Acad Sci USA 92 (9), 3726 - 30. |
| [128] | Batista D G., et al. (2010) Biological, ultrastructural effect and subcellular localization of aromatic diamidines in Trypanosoma cruzi. Parasitol 137 (2), 251 - 9. |
| [129] | Sanz-Rodríguez C E, Concepción J L, Pekerar S, Oldfield E, Urbina J A. (2007) Bisphosphonates as inhibitors of Trypanosoma cruzi hexokinase: kinetic and metabolic studies. J Biol Chem 282 (17), 12377 - 87. |
| [130] | Urbina J A. (2010) Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches. Acta Trop 115 (1-2), 55 - 68. |
| [131] | Hudock P M, et al. (2006) Inhibition of Trypanosoma cruzi hexokinase by bisphosphonates. J Med Chem 49 (1), 215 – 23. |
| [132] | Klebe G., Abraham U, Mietzner T. (1994) Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J Med Chem 37 (24), 4130 - 46. |
| [133] | Bakker M B, Westerhoff V H, Opperdoes R F, Michels A M P. (2000) Metabolic control analysis of glycolysis in trypanosomes as an approach to improve selectivity and effectiveness of drugs. Molec Biochem Parasitol 106 (1), 1 - 10. |
| [134] | Urbina J A, Crespo A. (1984) Regulation of energy metabolism in Trypanosoma (schizotrypanum) cruzi epimastigotes, I. Hexokinase and phosphofructokinase. Mol Biochem Parasitol 11, 225–239. |
| [135] | Leitão A, et al. (2004) Structure-activity relationships of novel inhibitors of glyceraldehyde-3-phosphate dehydrogenase. Bioorg Med Chem Letters 14 (9), 2199 - 204. |
| [136] | Silva J J N, Osakabe A L, Pavanelli W R, Silva J S, Franco D. (2007) In vitro and in vivo antiproliferative and trypanocidal activities of ruthenium NO donors. Br J Pharmacol 152 (1), 112 – 21. |
| [137] | Neres J, et al. (2007) Benzoic acid and pyridine derivatives as inhibitors of Trypanosoma cruzi trans-sialidase. Bioorg Med Chem 15 (5), 2106 - 19. |
| [138] | Alvarado A C, Martínez Z F, Páez R L, Nogueda B, Baeza I, Wong C. (2007). In vitro and in vivo trypanocidal activity of the ethyl esters of N-allyl and N-propyl oxamates using different Trypanosoma cruzi strains. J Enzym Inhib Med Chem 22 (2), 227 - 33. |
| [139] | Alvarado A C, et al. (2010) Trypanocidal activity of the ethyl esters of N-propyl and N-isopropyl oxamates on intracellular amastigotes of Trypanosoma cruzi acute infected mice. J Enzym Inhib Med Chem 25 (1), 111 - 5. |
| [140] | Chena M A, Elizondo-Jiménez S, Rodríguez-Páez L, Nogueda-Torres B, Baeza-Ramírez I, Wong-Ramírez C. (2004) Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes. Mem Inst Oswaldo Cruz 99 (8), 831 - 7. |
| [141] | Alloatti A, Uttaro A D. (2010) Highly specific methyl-end fatty-acid desaturases of trypanosomatids. Mol Biochem Parasitol 175 (2), 126 - 32. |
| [142] | Alloatti A, Testero S A, Uttaro A D. (2009) Chemical evaluation of fatty acid desaturases as drug targets in Trypanosoma cruzi. Int J Parasitol 39 (9), 985 - 93. |
| [143] | Cheleski J, et al. (2010) Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery. Eur J Med Chem 45 (12), 5899 - 909. |
| [144] | Rocha O P, et al. (2011) Chemical Profile and Biological Potential of Non-Polar Fractions from Centroceras clavulatum (C. Agardh) Montagne (Ceramiales, Rhodophyta). Molecules. 16 (8), 7105 – 14. |
| [145] | Barbosa C F, Okuda E S, Chung M C, Ferreira E I, Cicarelli R M B. (2007) Rapid test for the evaluation of the activity of the prodrug hydroxymethylnitrofurazone in the processing of Trypanosoma cruzi messenger RNAs. Braz J Med Biol Res 40 (1), 33 - 9. |
| [146] | Harkiolaki M, Dodson E J, Bernier-Villamor V, Turkenburg J P, González-Pacanowska D, Wilson K S. (2004) The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/ dUDP binding fold. Structure 12 (1), 41 - 53. |
| [147] | Gilbert I H. (2002) Inhibitors of dihydrofolate reductase in leishmania and trypanosomes. Biochem. Biophys. Acta 1587 (2-3), 249 - 57. |
| [148] | Zuccotto F, et al. (2001) Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase. Eur J Med Chem 36 (5), 395 - 405. |
| [149] | Zuccotto F, Brun R, Gonzalez-Pacanowska D, Ruiz-Perez L M, Gilbert I H. (1999) The structure-based design and synthesis of selective inhibitors of Trypanosoma cruzi dihydrofolate reductase. Bioorg Med Chem Lett 9 (10), 1463 - 8. |
| [150] | Chowdhury S F, et al. (1999) Design, Synthesis, and Evaluation of Inhibitors of Trypanosomal and Leishmanial Dihydrofolate Reductase. J Med Chem 42 (21), 4300 - 12. |
| [151] | Khabnadideh S, et al. (2005) Design, synthesis and evaluation of 2,4-diaminoquinazolines as inhibitors of trypanosomal and leishmanial dihydrofolate reductase. Bioorg Med Chem 13 (7), 2637 - 49. |
| [152] | Schormann N, et al. (2010) Synthesis and characterization of potent inhibitors of Trypanosoma cruzi dihydrofolate reductase. Bioorg Med Chem 18 (11), 4056 - 66. |
| [153] | Palma A, Yepes A F, Leal S M, Coronado C A, Escobar P. (2009) Synthesis and in vitro activity of new tetrahydronaphtho[1,2-b]azepine derivatives against Trypanosoma cruzi and Leishmania chagasi parasites. Bioorg Med Chem Letters 19 (8), 2360 - 3. |
| [154] | Souza D H, et al. (1998) Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase: structure, catalytic mechanism and targeted inhibitor design. FEBS Lett 424 (3), 131 - 5. |
| [155] | Silva J J N, et al. (2010) Novel ruthenium complexes as potential drugs for Chagas's disease: enzyme inhibition and in vitro/in vivo trypanocidal activity. British J Pharmacol 160 (2), 260 – 9. |
| [156] | Tomazela D M, et al. (2000) Pyrano chalcones and flavone from Neoraputia magnífica and their Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase-inhibitory activities. Phytochem 55 (6), 643 - 51. |
| [157] | Bressi C J, et al. (2001) Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design Med Chem 44 (13), 2080 – 93. |
| [158] | Ladame S, et al. (2003) Crystal structure of Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase complexed with an analogue of 1,3-bisphospho-D-glyceric acid. Eur J Biochem 270 (22), 4574 – 86. |
| [159] | De Marchi A A, et al. (2004) New 3-piperonylcoumarins as inhibitors of glycosomal glyceraldehyde-3- phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi. Bioorg Med Chem 12 (18), 4823 - 33. |
| [160] | Pereira J M, et al. (2008) Anacardic acid derivatives as inhibitors of glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi. Bioorg Med Chem 16 (19), 8889 - 95. |
| [161] | Coura R J, De Castro L S. (2002) A Critical Review on Chagas Disease Chemotherapy. Mem Inst Oswaldo Cruz 97 (1), 3 - 24. |
| [162] | Trossini G H G. (2004) Antichagásicos potenciais: síntese de bases de Mannich do hidroximetilnitrofural. Dissertation. University of São Paulo, Pharmaceutical Science Program. |
| [163] | Guimarães S A D, Faria R A. (2007) Substâncias da natureza com atividade anti-Trypanosoma cruzi. Braz J Pharmacogn 17 (3), 455 - 65. |
| [164] | Leite J R, et al. (2005) Phylloseptins: a novel class of anti-bacterial and anti-protozoan peptides from the Phyllomedusa genus. Peptides 26 (4), 565 - 73. |
| [165] | Adade C M, Chagas G S F, Souto-Padrón T. (2012) Apis mellifera venom induces different cell death pathways in Trypanosoma cruzi. Parasitol 139 (11), 1444 - 61. |
| [166] | Basombrío M A, Besuschio S. (1982) Trypanosoma cruzi culture used as vaccine to prevent chronic Chagas' disease in mice. Infect Immun 36 (1), 351 – 6. |
| [167] | Acosta A M, Santos-Buch C A. (1985) Autoimmune myocarditis induced by Trypanosoma cruzi. Circulation. 71 (6), 1255 - 61. |
| [168] | Planelles L, Thomas M C, Alonso C, López M C. (2001) DNA Immunization with Trypanosoma cruzi HSP70 Fused to the KMP11 Protein Elicits a Cytotoxic and Humoral Immune Response against the Antigen and Leads to Protection. Infect Immun 69 (10), 6558 – 63. |
| [169] | Garg N, Tarleton R L. (2002) Genetic immunization elicits antigen-specific protective immune responses and decreases disease severity in Trypanosoma cruzi infection. Infect Immun 70 (10), 5547 - 55. |
| [170] | Laucella S A, et al. (2004) Frequency of interferon-γ-producing T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human chagas disease. J Infect Dis 189 (5), 909 - 18. |
| [171] | Machado A V, Cardoso J E, Claser C, Rodrigues M M, Gazzinelli R T, Bruna-Romero O. (2006) Long-term protective immunity induced against Trypanosoma cruzi infection after vaccination with recombinant adenoviruses encoding amastigote surface protein-2 and trans-sialidase. Hum Gene Ther 17 (9), 898 - 908. |
APA Style
Viviane M. de Oliveira, Luana T. Mendes, Durinézio J. Almeida, Lucas V. B. Hoelz, Pedro H. M. Torres, et al. (2014). New Treatments for Chagas Disease and the Relationship between Chagasic Patients and Cancers. Cancer Research Journal, 2(6-1), 11-29. https://doi.org/10.11648/j.crj.s.2014020601.12
ACS Style
Viviane M. de Oliveira; Luana T. Mendes; Durinézio J. Almeida; Lucas V. B. Hoelz; Pedro H. M. Torres, et al. New Treatments for Chagas Disease and the Relationship between Chagasic Patients and Cancers. Cancer Res. J. 2014, 2(6-1), 11-29. doi: 10.11648/j.crj.s.2014020601.12
AMA Style
Viviane M. de Oliveira, Luana T. Mendes, Durinézio J. Almeida, Lucas V. B. Hoelz, Pedro H. M. Torres, et al. New Treatments for Chagas Disease and the Relationship between Chagasic Patients and Cancers. Cancer Res J. 2014;2(6-1):11-29. doi: 10.11648/j.crj.s.2014020601.12
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Download@article{10.11648/j.crj.s.2014020601.12,
author = {Viviane M. de Oliveira and Luana T. Mendes and Durinézio J. Almeida and Lucas V. B. Hoelz and Pedro H. M. Torres and Pedro Geraldo Pascutti and Guilherme Barroso L. de Freitas},
title = {New Treatments for Chagas Disease and the Relationship between Chagasic Patients and Cancers},
journal = {Cancer Research Journal},
volume = {2},
number = {6-1},
pages = {11-29},
doi = {10.11648/j.crj.s.2014020601.12},
url = {https://doi.org/10.11648/j.crj.s.2014020601.12},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.s.2014020601.12},
abstract = {Chagas disease is an infectious illness with a broad distribution throughout the South American and African continents, importantly influencing human morbidity and mortality and a controversial relationship with the onset of cancers, especially of the gastrointestinal tract system. In addition, it is listed by the World Health Organization (WHO) as one ofthe most neglected tropical diseases. Although Chagas disease (CD) was discovered more than 100 years ago, the existing therapies show low efficacy and serious side effects and developing safer and more effective drugs remains a hard challenge. Thus, this review highlights the main, novel and promising treatments against Trypanosoma cruzi, including biomacromolecules, natural products, vaccines, and metabolic pathway targets and highlights a worsening of esophageal cancer prognosis in chagasic patients. Moreover, we also discuss the perspectives of obtaining original optimized drugs that take advantage of organic and inorganic medicinal chemistry advances, as well as molecular modeling and biotechnology.},
year = {2014}
}
TY - JOUR T1 - New Treatments for Chagas Disease and the Relationship between Chagasic Patients and Cancers AU - Viviane M. de Oliveira AU - Luana T. Mendes AU - Durinézio J. Almeida AU - Lucas V. B. Hoelz AU - Pedro H. M. Torres AU - Pedro Geraldo Pascutti AU - Guilherme Barroso L. de Freitas Y1 - 2014/12/27 PY - 2014 N1 - https://doi.org/10.11648/j.crj.s.2014020601.12 DO - 10.11648/j.crj.s.2014020601.12 T2 - Cancer Research Journal JF - Cancer Research Journal JO - Cancer Research Journal SP - 11 EP - 29 PB - Science Publishing Group SN - 2330-8214 UR - https://doi.org/10.11648/j.crj.s.2014020601.12 AB - Chagas disease is an infectious illness with a broad distribution throughout the South American and African continents, importantly influencing human morbidity and mortality and a controversial relationship with the onset of cancers, especially of the gastrointestinal tract system. In addition, it is listed by the World Health Organization (WHO) as one ofthe most neglected tropical diseases. Although Chagas disease (CD) was discovered more than 100 years ago, the existing therapies show low efficacy and serious side effects and developing safer and more effective drugs remains a hard challenge. Thus, this review highlights the main, novel and promising treatments against Trypanosoma cruzi, including biomacromolecules, natural products, vaccines, and metabolic pathway targets and highlights a worsening of esophageal cancer prognosis in chagasic patients. Moreover, we also discuss the perspectives of obtaining original optimized drugs that take advantage of organic and inorganic medicinal chemistry advances, as well as molecular modeling and biotechnology. VL - 2 IS - 6-1 ER -
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