Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Polypharmacology in the Treatment of Chagas Disease

Author(s): Elena Aguilera, Guzmán Alvarez, Hugo Cerecetto* and Mercedes González *

Volume 26, Issue 23, 2019

Page: [4476 - 4489] Pages: 14

DOI: 10.2174/0929867325666180410101728

Price: $65

Abstract

The current treatment of Chagas disease is based on monopharmacology where the used drugs have limited efficacy and severe side effects. In order to overcome these limitations, some tools have been described including the development or isolation of new drugs, drug repositioning, and polypharmacology. Here, we review the polypharmacology strategy where compounds belonging to different structural chemotypes were combined in order to affect different biochemical pathways of T. cruzi parasite. Therefore ergosterol biosynthesis inhibitors, anti-inflammatory agents, cardiac dysfunction drugs, trypanothione reductase inhibitors, vitamins, between others, were combined looking for new anti-Chagas treatment. Natural products were also used in the application of this strategy.

Keywords: Chagas disease, polypharmacology, synergism, antagonism, isobologram, cardiac dysfunction drugs.

« Previous
[1]
Nouvellet, P.; Cucunubá, Z.M.; Gourbière, S. Ecology, evolution and control of Chagas disease: a century of neglected modelling and a promising future. Adv. Parasitol., 2015, 87, 135-191.
[http://dx.doi.org/10.1016/bs.apar.2014.12.004] [PMID: 25765195]
[2]
Kapelusznik, L.; Varela, D.; Montgomery, S.P.; Shah, A.N.; Steurer, F.J.; Rubinstein, D.; Caplivski, D.; Pinney, S.P.; Turker, D.; Factor, S.H. Chagas disease in Latin American immigrants with dilated cardiomyopathy in New York City. Clin. Infect. Dis., 2013, 57(1)e7
[http://dx.doi.org/10.1093/cid/cit199] [PMID: 23537911]
[3]
Bahia, M.T. Diniz, Lde.F.; Mosqueira, V.C. Therapeutical approaches under investigation for treatment of Chagas disease. Expert Opin. Investig. Drugs, 2014, 23(9), 1225-1237.
[http://dx.doi.org/10.1517/13543784.2014.922952] [PMID: 24855989]
[4]
Cerecetto, H.; González, M. Synthetic medicinal chemistry in Chagas’ disease: Compounds at the final stage of “Hit-to-Lead” phase. Pharmaceuticals (Basel), 2010, 3(4), 810-838.
[http://dx.doi.org/10.3390/ph3040810] [PMID: 27713281]
[5]
González, M.; Cerecetto, H. Novel compounds to combat trypanosomatid infections: a medicinal chemical perspective. Expert Opin. Ther. Pat., 2011, 21(5), 699-715.
[http://dx.doi.org/10.1517/13543776.2011.565334] [PMID: 21428846]
[6]
Docampo, R.; Moreno, S.N.J.; Turrens, J.F.; Katzin, A.M.; Gonzalez-Cappa, S.M.; Stoppani, A.O.M. Biochemical and ultrastructural alterations produced by miconazole and econazole in Trypanosoma cruzi. Mol. Biochem. Parasitol., 1981, 3(3), 169-180.
[http://dx.doi.org/10.1016/0166-6851(81)90047-5] [PMID: 6265775]
[7]
Beach, D.H.; Goad, L.J.; Holz, G.G., Jr Effects of ketoconazole on sterol biosynthesis by Trypanosoma cruzi epimastigotes. Biochem. Biophys. Res. Commun., 1986, 136(3), 851-856.
[http://dx.doi.org/10.1016/0006-291X(86)90410-9] [PMID: 3521598]
[8]
Larralde, G.; Vivas, J.; Urbina, J.A. Concentration and time dependence of the effects of ketoconazole on growth and sterol synthesis by Trypanosoma (Schizotrypanum) cruzi epimastigotes. Acta Cient. Venez., 1988, 39(2), 140-146.
[PMID: 3075103]
[9]
Van den Bossche, H.; Willemsens, G.; Cools, W.; Cornelissen, F.; Lauwers, W.F.; van Cutsem, J.M. In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis. Antimicrob. Agents Chemother., 1980, 17(6), 922-928.
[http://dx.doi.org/10.1128/AAC.17.6.922] [PMID: 6250469]
[10]
Urbina, J.A.; 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(2), 185-195.
[http://dx.doi.org/10.1016/0166-6851(88)90111-9] [PMID: 2845268]
[11]
Urbina, J.A.; Lazardi, K.; Aguirre, T.; Piras, M.M.; Piras, R. Antiproliferative synergism of the allylamine SF 86-327 and ketoconazole on epimastigotes and amastigotes of Trypanosoma (Schizotrypanum) cruzi. Antimicrob. Agents Chemother., 1988, 32(8), 1237-1242.
[http://dx.doi.org/10.1128/AAC.32.8.1237] [PMID: 3056256]
[12]
Lazardi, K.; Urbina, J.A.; 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(11), 2097-2105.
[http://dx.doi.org/10.1128/AAC.34.11.2097] [PMID: 2073100]
[13]
Maldonado, R.A.; Molina, J.; Payares, G.; Urbina, J.A. Experimental chemotherapy with combinations of ergosterol biosynthesis inhibitors in murine models of Chagas’ disease. Antimicrob. Agents Chemother., 1993, 37(6), 1353-1359.
[http://dx.doi.org/10.1128/AAC.37.6.1353] [PMID: 8328786]
[14]
Ryley, J.F.; McGregor, S.; Wilson, R.G. Activity of ICI 195,739--a novel, orally active bistriazole--in rodent models of fungal and protozoal infections. Ann. N. Y. Acad. Sci., 1988, 544, 310-328.
[http://dx.doi.org/10.1111/j.1749-6632.1988.tb40416.x] [PMID: 3214071]
[15]
Urbina, J.A.; Lazardi, K.; Aguirre, T.; Piras, M.M.; Piras, R. Antiproliferative effects and mechanism of action of ICI 195,739, a novel bis-triazole derivative, on epimastigotes and amastigotes of Trypanosoma (Schizotrypanum) cruzi. Antimicrob. Agents Chemother., 1991, 35(4), 730-735.
[http://dx.doi.org/10.1128/AAC.35.4.730] [PMID: 2069379]
[16]
Lazardi, K.; Urbina, J.A.; de Souza, W. Ultrastructural alterations induced by ICI 195,739, a bis-triazole derivative with strong antiproliferative action against Trypanosoma (Schizotrypanum) cruzi. Antimicrob. Agents Chemother., 1991, 35(4), 736-740.
[http://dx.doi.org/10.1128/AAC.35.4.736] [PMID: 2069380]
[17]
Urbina, J.A.; Lazardi, K.; Aguirre, T.; Piras, M.M.; Piras, R. Antiproliferative effects and mechanism of action of ICI 195,739, a novel bis-triazole derivative, on epimastigotes and amastigotes of Trypanosoma (Schizotrypanum) cruzi. Antimicrob. Agents Chemother., 1991, 35(4), 730-735.
[http://dx.doi.org/10.1128/AAC.35.4.730] [PMID: 2069379]
[18]
Araújo, M.S.; Martins-Filho, O.A.; Pereira, M.E.; Brener, Z. A combination of benznidazole and ketoconazole enhances efficacy of chemotherapy of experimental Chagas’ disease. J. Antimicrob. Chemother., 2000, 45(6), 819-824.
[http://dx.doi.org/10.1093/jac/45.6.819] [PMID: 10837436]
[19]
Diniz, Lde. F.; Urbina, J.A.; de Andrade, I.M.; Mazzeti, A.L.; Martins, T.A.F.; Caldas, I.S.; Talvani, A.; Ribeiro, I.; Bahia, M.T. Benznidazole and posaconazole in experimental Chagas disease: positive interaction in concomitant and sequential treatments. PLoS Negl. Trop. Dis., 2013, 7(8)e2367
[http://dx.doi.org/10.1371/journal.pntd.0002367] [PMID: 23967360]
[20]
Molina, J.; Martins-Filho, O.; Brener, Z.; Romanha, A.J.; Loebenberg, D.; Urbina, J.A. Activities of the triazole derivative SCH 56592 (posaconazole) against drug-resistant strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi in immunocompetent and immunosuppressed murine hosts. Antimicrob. Agents Chemother., 2000, 44(1), 150-155.
[http://dx.doi.org/10.1128/AAC.44.1.150-155.2000] [PMID: 10602737]
[21]
Assíria Fontes Martins, T.; de Figueiredo Diniz, L.; Mazzeti, A.L.; da Silva do Nascimento, A.F.; Caldas, S.; Caldas, I.S.; de Andrade, I.M.; Ribeiro, I.; Bahia, M.T. Benznidazole/itraconazole combination treatment enhances anti-Trypanosoma cruzi activity in experimental Chagas disease. PLoS One, 2015, 10(6)e0128707
[http://dx.doi.org/10.1371/journal.pone.0128707] [PMID: 26076455]
[22]
Urbina, J.A.; Vivas, J.; Visbal, G.; Contreras, L.M. Modification of the sterol composition of Trypanosoma (Schizotrypanum) cruzi epimastigotes by delta 24(25)-sterol methyl transferase inhibitors and their combinations with ketoconazole. Mol. Biochem. Parasitol., 1995, 73(1-2), 199-210.
[http://dx.doi.org/10.1016/0166-6851(95)00117-J] [PMID: 8577328]
[23]
Vivas, J.; Urbina, J.A.; de Souza, W. Ultrastructural alterations in Trypanosoma (Schizotrypanum) cruzi induced by Delta(24(25)) sterol methyl transferase inhibitors and their combinations with ketoconazole. Int. J. Antimicrob. Agents, 1997, 8(1), 1-6.
[http://dx.doi.org/10.1016/S0924-8579(96)00345-7] [PMID: 18611778]
[24]
Florin-Christensen, M.; Florin-Christensen, J.; Garin, C.; Isola, E.; Brenner, R.R.; Rasmussen, L. Inhibition of Trypanosoma cruzi growth and sterol biosynthesis by lovastatin. Biochem. Biophys. Res. Commun., 1990, 166(3), 1441-1445.
[http://dx.doi.org/10.1016/0006-291X(90)91028-Q] [PMID: 2407242]
[25]
Urbina, J.A.; Lazardi, K.; Marchan, E.; Visbal, G.; Aguirre, T.; Piras, M.M.; Piras, R.; Maldonado, R.A.; Payares, G.; de Souza, W. Mevinolin (lovastatin) potentiates the antiproliferative effects of ketoconazole and terbinafine against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies. Antimicrob. Agents Chemother., 1993, 37(3), 580-591.
[http://dx.doi.org/10.1128/AAC.37.3.580] [PMID: 8460926]
[26]
Lira, R.; Contreras, L.M.; Rita, R.M.; Urbina, J.A. Mechanism of action of anti-proliferative lysophospholipid analogues against the protozoan parasite Trypanosoma cruzi: potentiation of in vitro activity by the sterol biosynthesis inhibitor ketoconazole. J. Antimicrob. Chemother., 2001, 47(5), 537-546.
[http://dx.doi.org/10.1093/jac/47.5.537] [PMID: 11328763]
[27]
Bhattacharya, S.K.; Sinha, P.K.; Sundar, S.; Thakur, C.P.; Jha, T.K.; Pandey, K.; Das, V.R.; Kumar, N.; Lal, C.; Verma, N.; Singh, V.P.; Ranjan, A.; Verma, R.B.; Anders, G.; Sindermann, H.; Ganguly, N.K. Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis. J. Infect. Dis., 2007, 196(4), 591-598.
[http://dx.doi.org/10.1086/519690] [PMID: 17624846]
[28]
Luna, K.P.; Hernández, I.P.; Rueda, C.M.; Zorro, M.M.; Croft, S.L.; Escobar, P. In vitro susceptibility of Trypanosoma cruzi strains from Santander, Colombia, to hexadecylphosphocholine (miltefosine), nifurtimox and benznidazole. Biomedica, 2009, 29(3), 448-455.
[http://dx.doi.org/10.7705/biomedica.v29i3.15] [PMID: 20436996]
[29]
Santa-Rita, R.M.; Lira, R.; Barbosa, H.S.; Urbina, J.A.; de Castro, S.L. Anti-proliferative synergy of lysophospholipid analogues and ketoconazole against Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae): cellular and ultrastructural analysis. J. Antimicrob. Chemother., 2005, 55(5), 780-784.
[http://dx.doi.org/10.1093/jac/dki087] [PMID: 15790672]
[30]
Andrade, S.G.; Andrade, Z.A.; Sadigursky, M. Combined treatment with a nitrofuranic and a corticoid in experimental Chagas’ disease in the dog. Am. J. Trop. Med. Hyg., 1980, 29(5), 766-773.
[http://dx.doi.org/10.4269/ajtmh.1980.29.766] [PMID: 6776831]
[31]
Rassi, A.; Amato Neto, V.; de Siqueira, A.F.; Ferriolli Filho, F.; Amato, V.S.; Rassi, G.G.; Rassi, Junior, A. Treatment of chronic Chagas’ disease with an association of nifurtimox and corticoid. Rev. Soc. Bras. Med. Trop., 2002, 35(6), 547-550.
[http://dx.doi.org/10.1590/S0037-86822002000600001] [PMID: 12612733]
[32]
Michelin, M.A.; Silva, J.S.; Cunha, F.Q. Inducible cyclooxygenase released prostaglandin mediates immunosuppression in acute phase of experimental Trypanosoma cruzi infection. Exp. Parasitol., 2005, 111(2), 71-79.
[http://dx.doi.org/10.1016/j.exppara.2005.05.001] [PMID: 16009364]
[33]
Hideko Tatakihara, V.L.; Cecchini, R.; Borges, C.L.; Malvezi, A.D.; Graça-de Souza, V.K.; Yamada-Ogatta, S.F.; Rizzo, L.V.; Pinge-Filho, P. Effects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murine Trypanosoma cruzi infection. FEMS Immunol. Med. Microbiol., 2008, 52(1), 47-58.
[http://dx.doi.org/10.1111/j.1574-695X.2007.00340.x] [PMID: 18031539]
[34]
Santos, E.C.; Novaes, R.D.; Bastos, D.S.S.; Oliveira, J.M.; Penitente, A.R.; Gonçalves, W.G.; Cardoso, S.A.; Talvani, A.; Oliveira, L.L. Modulation of oxidative and inflammatory cardiac response by nonselective 1- and 2-cyclooxygenase inhibitor and benznidazole in mice. J. Pharm. Pharmacol., 2015, 67(11), 1556-1566.
[http://dx.doi.org/10.1111/jphp.12451] [PMID: 26105111]
[35]
Campos-Estrada, C.; Liempi, A.; González-Herrera, F.; Lapier, M.; Kemmerling, U.; Pesce, B.; Ferreira, J.; López-Muñoz, R.; Maya, J.D. Simvastatin and benznidazole-mediated prevention of Trypanosoma cruzi-induced endothelial activation: Role of 15-epi-lipoxin A4 in the action of simvastatin. PLoS Negl. Trop. Dis., 2015, 9(5)e0003770
[http://dx.doi.org/10.1371/journal.pntd.0003770] [PMID: 25978361]
[36]
Benaim, G.; Sanders, J.M.; Garcia-Marchán, Y.; Colina, C.; Lira, R.; Caldera, A.R.; Payares, G.; Sanoja, C.; Burgos, J.M.; Leon-Rossell, A.; Concepcion, J.L.; Schijman, A.G.; Levin, M.; Oldfield, E.; Urbina, J.A. Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole. J. Med. Chem., 2006, 49(3), 892-899.
[http://dx.doi.org/10.1021/jm050691f] [PMID: 16451055]
[37]
Veiga-Santos, P.; Barrias, E.S.; Santos, J.F.C.; de Barros Moreira, T.L.; de Carvalho, T.M.; Urbina, J.A.; de Souza, W. Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi. Int. J. Antimicrob. Agents, 2012, 40(1), 61-71.
[http://dx.doi.org/10.1016/j.ijantimicag.2012.03.009] [PMID: 22591838]
[38]
Paniz-Mondolfi, A.E.; Pérez-Alvarez, A.M.; Lanza, G.; Márquez, E.; Concepción, J.L. Amiodarone and itraconazole: a rational therapeutic approach for the treatment of chronic Chagas’ disease. Chemotherapy, 2009, 55(4), 228-233.
[http://dx.doi.org/10.1159/000219436] [PMID: 19451712]
[39]
Planer, J.D.; Hulverson, M.A.; Arif, J.A.; Ranade, R.M.; Don, R.; Buckner, F.S. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi. PLoS Negl. Trop. Dis., 2014, 8(7)e2977
[http://dx.doi.org/10.1371/journal.pntd.0002977] [PMID: 25033456]
[40]
de Paula Costa, G.; Silva, R.R.; Pedrosa, M.C.; Pinho, V.; de Lima, W.G.; Teixeira, M.M.; Bahia, M.T.; Talvani, A. Enalapril prevents cardiac immune-mediated damage and exerts anti-Trypanosoma cruzi activity during acute phase of experimental Chagas disease. Parasite Immunol., 2010, 32(3), 202-208.
[http://dx.doi.org/10.1111/j.1365-3024.2009.01179.x] [PMID: 20398183]
[41]
Penitente, A.R.; Leite, A.L.; de Paula Costa, G.; Shrestha, D.; Horta, A.L.; Natali, A.J.; Neves, C.A.; Talvani, A. Enalapril in combination with benznidazole reduces cardiac inflammation and creatine kinases in mice chronically infected with Trypanosoma cruzi. Am. J. Trop. Med. Hyg., 2015, 93(5), 976-982.
[http://dx.doi.org/10.4269/ajtmh.15-0237] [PMID: 26350447]
[42]
Pereira, I.R.; Vilar-Pereira, G.; Moreira, O.C.; Ramos, I.P.; Gibaldi, D.; Britto, C.; Moraes, M.O.; Lannes-Vieira, J. Pentoxifylline reverses chronic experimental Chagasic cardiomyopathy in association with repositioning of abnormal CD8+ T-cell response. PLoS Negl. Trop. Dis., 2015, 9(3)e0003659
[http://dx.doi.org/10.1371/journal.pntd.0003659] [PMID: 25789471]
[43]
Vilar-Pereira, G.; Resende Pereira, I.; de Souza Ruivo, L.A.; Cruz Moreira, O.; da Silva, A.A.; Britto, C.; Lannes-Vieira, J. Combination chemotherapy with suboptimal doses of benznidazole and pentoxifylline sustains partial reversion of experimental Chagas’ heart disease. Antimicrob. Agents Chemother., 2016, 60(7), 4297-4309.
[http://dx.doi.org/10.1128/AAC.02123-15] [PMID: 27161638]
[44]
Rivarola, H.W.; Fernández, A.R.; Enders, J.E.; Fretes, R.; Gea, S.; Paglini-Oliva, P. Effects of clomipramine on Trypanosoma cruzi infection in mice. Trans. R. Soc. Trop. Med. Hyg., 2001, 95(5), 529-533.
[http://dx.doi.org/10.1016/S0035-9203(01)90029-X] [PMID: 11706667]
[45]
Roufogalis, B.D.; Minocherhomjee, A.M.; Al-Jobore, A. Pharmacological antagonism of calmodulin. Can. J. Biochem. Cell Biol., 1983, 61(8), 927-933.
[http://dx.doi.org/10.1139/o83-118] [PMID: 6138140]
[46]
Benson, T.J.; McKie, J.H.; Garforth, J.; Borges, A.; Fairlamb, A.H.; Douglas, K.T. Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures. Biochem. J., 1992, 286(Pt 1), 9-11.
[http://dx.doi.org/10.1042/bj2860009] [PMID: 1355650]
[47]
Fauro, R.; Lo Presti, S.; Bazán, C.; Baez, A.; Strauss, M.; Triquell, F.; Cremonezzi, D.; Negrete, O.S.; Willhuber, G.C.; Paglini-Oliva, P.; Rivarola, H.W. Use of clomipramine as chemotherapy of the chronic phase of Chagas disease. Parasitology, 2013, 140(7), 917-927.
[http://dx.doi.org/10.1017/S0031182013000103] [PMID: 23534690]
[48]
Gobbi, P.; Baez, A.; Lo Presti, M.S.; Fernández, A.R.; Enders, J.E.; Fretes, R.; Gea, S.; Paglini-Oliva, P.A.; Rivarola, H.W. Association of clomipramine and allopurinol for the treatment of the experimental infection with Trypanosoma cruzi. Parasitol. Res., 2010, 107(5), 1279-1283.
[http://dx.doi.org/10.1007/s00436-010-2002-z] [PMID: 20680335]
[49]
Strauss, M.; Lo Presti, M.S.; Bazán, P.C.; Baez, A.; Fauro, R.; Esteves, B.; Sanchez Negrete, O.; Cremonezzi, D.; Paglini-Oliva, P.A.; Rivarola, H.W. Clomipramine and benznidazole association for the treatment of acute experimental Trypanosoma cruzi infection. Parasitol. Int., 2013, 62(3), 293-299.
[http://dx.doi.org/10.1016/j.parint.2013.02.004] [PMID: 23500720]
[50]
García, M.C.; Ponce, N.E.; Sanmarco, L.M.; Manzo, R.H.; Jimenez-Kairuz, A.F.; Aoki, M.P. Clomipramine and benznidazole act synergistically and ameliorate the outcome of experimental Chagas disease. Antimicrob. Agents Chemother., 2016, 60(6), 3700-3708.
[http://dx.doi.org/10.1128/AAC.00404-16] [PMID: 27067322]
[51]
Soeiro, M.N.; De Souza, E.M.; Stephens, C.E.; Boykin, D.W. Aromatic diamidines as antiparasitic agents. Expert Opin. Investig. Drugs, 2005, 14(8), 957-972.
[http://dx.doi.org/10.1517/13543784.14.8.957] [PMID: 16050790]
[52]
Díaz, M.V.; Miranda, M.R.; Campos-Estrada, C.; Reigada, C.; Maya, J.D.; Pereira, C.A.; López-Muñoz, R. Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activity and inhibits the polyamine transport in Trypanosoma cruzi. Acta Trop., 2014, 134, 1-9.
[http://dx.doi.org/10.1016/j.actatropica.2014.02.012] [PMID: 24560964]
[53]
Batista, Dda. G.; Batista, M.M.; de Oliveira, G.M.; Britto, C.C.; Rodrigues, A.C.M.; Stephens, C.E.; Boykin, D.W.; Soeiro, Mde.N. Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo. PLoS One, 2011, 6(7)e22155
[http://dx.doi.org/10.1371/journal.pone.0022155] [PMID: 21814568]
[54]
da Silva, C.F. Batista, Dda.G.; Oliveira, G.M.; de Souza, E.M.; Hammer, E.R.; da Silva, P.B.; Daliry, A.; Araujo, J.S.; Britto, C.; Rodrigues, A.C.; Liu, Z.; Farahat, A.A.; Kumar, A.; Boykin, D.W.; Soeiro, Mde.N. In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection. PLoS One, 2012, 7(1)e30356
[http://dx.doi.org/10.1371/journal.pone.0030356] [PMID: 22291940]
[55]
Seguel, V.; Castro, L.; Reigada, C.; Cortes, L.; Díaz, M.V.; Miranda, M.R.; Pereira, C.A.; Lapier, M.; Campos-Estrada, C.; Morello, A.; Kemmerling, U.; Maya, J.D.; López-Muñoz, R. Pentamidine antagonizes the benznidazole’s effect in vitro, and lacks of synergy in vivo: Implications about the polyamine transport as an anti-Trypanosoma cruzi target. Exp. Parasitol., 2016, 171, 23-32.
[http://dx.doi.org/10.1016/j.exppara.2016.10.007] [PMID: 27729250]
[56]
Ciccarelli, A.; Araujo, L.; Batlle, A.; Lombardo, E. Effect of haemin on growth, protein content and the antioxidant defence system in Trypanosoma cruzi. Parasitology, 2007, 134(Pt 7), 959-965.
[http://dx.doi.org/10.1017/S0031182007002399] [PMID: 17316475]
[57]
Ciccarelli, A.B.; Frank, F.M.; Puente, V.; Malchiodi, E.L.; Batlle, A.; Lombardo, M.E. Antiparasitic effect of vitamin B12 on Trypanosoma cruzi. Antimicrob. Agents Chemother., 2012, 56(10), 5315-5320.
[http://dx.doi.org/10.1128/AAC.00481-12] [PMID: 22869565]
[58]
Cristina Desoti, V.; Lazarin-Bidóia, D.; Martins Ribeiro, F.; Cardoso Martins, S.; da Silva Rodrigues, J.H.; Ueda-Nakamura, T.; Vataru Nakamura, C.; Farias Ximenes, V.; de Oliveira Silva, S. The combination of vitamin K3 and vitamin C has synergic activity against forms of Trypanosoma cruzi through a redox imbalance process. PLoS One, 2015, 10(12)e0144033
[http://dx.doi.org/10.1371/journal.pone.0144033] [PMID: 26641473]
[59]
Valdez, R.H.; Tonin, L.T.; Ueda-Nakamura, T.; Dias Filho, B.P.; Morgado-Diaz, J.A.; Sarragiotto, M.H.; Nakamura, C.V. Biological activity of 1,2,3,4-tetrahydro-beta-carboline-3-carboxamides against Trypanosoma cruzi. Acta Trop., 2009, 110(1), 7-14.
[http://dx.doi.org/10.1016/j.actatropica.2008.11.008] [PMID: 19063858]
[60]
Izumi, E.; Morello, L.G.; Ueda-Nakamura, T.; Yamada-Ogatta, S.F.; Filho, B.P.; Cortez, D.A.G.; Ferreira, I.C.P.; Morgado-Díaz, J.A.; Nakamura, C.V. Trypanosoma cruzi: antiprotozoal activity of parthenolide obtained from Tanacetum parthenium (L.) Schultz Bip. (Asteraceae, Compositae) against epimastigote and amastigote forms. Exp. Parasitol., 2008, 118(3), 324-330.
[http://dx.doi.org/10.1016/j.exppara.2007.08.015] [PMID: 17950283]
[61]
Pelizzaro-Rocha, K.J.; Tiuman, T.S.; Izumi, E.; Ueda-Nakamura, T.; Dias Filho, B.P.; Nakamura, C.V. Synergistic effects of parthenolide and benznidazole on Trypanosoma cruzi. Phytomedicine, 2010, 18(1), 36-39.
[http://dx.doi.org/10.1016/j.phymed.2010.09.005] [PMID: 21035317]
[62]
Izumi, E.; Ueda-Nakamura, T.; Veiga, V.F., Jr; Pinto, A.C.; Nakamura, C.V. Terpenes from Copaifera demonstrated in vitro antiparasitic and synergic activity. J. Med. Chem., 2012, 55(7), 2994-3001.
[http://dx.doi.org/10.1021/jm201451h] [PMID: 22440015]
[63]
Sandjo, L.P.; de Moraes, M.H.; Kuete, V.; Kamdoum, B.C.; Ngadjui, B.T.; Steindel, M. Individual and combined antiparasitic effect of six plant metabolites against Leishmania amazonensis and Trypanosoma cruzi. Bioorg. Med. Chem. Lett., 2016, 26(7), 1772-1775.
[http://dx.doi.org/10.1016/j.bmcl.2016.02.044] [PMID: 26906638]
[64]
Francisco, A.F.; de Abreu Vieira, P.M.; Arantes, J.M.; Pedrosa, M.L.; Martins, H.R.; Silva, M.; Veloso, V.M.; de Lana, M.; Bahia, M.T.; Tafuri, W.L.; Carneiro, C.M. Trypanosoma cruzi: effect of benznidazole therapy combined with the iron chelator desferrioxamine in infected mice. Exp. Parasitol., 2008, 120(4), 314-319.
[http://dx.doi.org/10.1016/j.exppara.2008.08.002] [PMID: 18789321]
[65]
Santos, C.D.; Toldo, M.P.; Santello, F.H. Filipin, Mdel.V.; Brazão, V.; do Prado Júnior, J.C. Dehydroepiandrosterone increases resistance to experimental infection by Trypanosoma cruzi. Vet. Parasitol., 2008, 153(3-4), 238-243.
[http://dx.doi.org/10.1016/j.vetpar.2008.01.039] [PMID: 18337011]
[66]
Santos, C.D.; Loria, R.M.; Oliveira, L.G.; Kuehn, C.C.; Toldo, M.P.; Albuquerque, S.; do Prado, J.C. Jr Effects of dehydroepiandrosterone-sulfate (DHEA-S) and benznidazole treatments during acute infection of two different Trypanosoma cruzi strains. Immunobiology, 2010, 215(12), 980-986.
[http://dx.doi.org/10.1016/j.imbio.2009.11.002] [PMID: 20163889]
[67]
Wen, J-J.; Gupta, S.; Guan, Z.; Dhiman, M.; Condon, D.; Lui, C.; Garg, N.J. Phenyl-α-tert-butyl-nitrone and benzonidazole treatment controlled the mitochondrial oxidative stress and evolution of cardiomyopathy in chronic chagasic Rats. J. Am. Coll. Cardiol., 2010, 55(22), 2499-2508.
[http://dx.doi.org/10.1016/j.jacc.2010.02.030] [PMID: 20510218]
[68]
Pérez-Silanes, S.; Torres, E.; Arbillaga, L.; Varela, J.; Cerecetto, H.; González, M.; Azqueta, A.; Moreno-Viguri, E. Synthesis and biological evaluation of quinoxaline di-N-oxide derivatives with in vitro trypanocidal activity. Bioorg. Med. Chem. Lett., 2016, 26(3), 903-906.
[http://dx.doi.org/10.1016/j.bmcl.2015.12.070] [PMID: 26750255]
[69]
Rodrigues, J.H.; Ueda-Nakamura, T.; Corrêa, A.G.; Sangi, D.P.; Nakamura, C.V. A quinoxaline derivative as a potent chemotherapeutic agent, alone or in combination with benznidazole, against Trypanosoma cruzi. PLoS One, 2014, 9(1)e85706
[http://dx.doi.org/10.1371/journal.pone.0085706] [PMID: 24465654]
[70]
Santos, E.C.; Novaes, R.D.; Cupertino, M.C.; Bastos, D.S.S.; Klein, R.C.; Silva, E.A.M.; Fietto, J.L.R.; Talvani, A.; Bahia, M.T.; Oliveira, L.L. Chemotherapy with Benznidazole and Suramin: applicability of their concomitant treatment in mice infected with a virulent strain of Trypanosoma cruzi. Antimicrob. Agents Chemother., 2015, 59, 5999-6006.
[http://dx.doi.org/10.1128/AAC.00779-15] [PMID: 26169419]
[71]
Novaes, R.D.; Sartini, M.V.P.; Rodrigues, J.P.F.; Gonçalves, R.V.; Santos, E.C.; Souza, R.L.M.; Caldas, I.S. Curcumin enhances the anti-Trypanosoma cruzi activity of benznidazole-based chemotherapy in acute experimental Chagas disease. Antimicrob. Agents Chemother., 2016, 60(6), 3355-3364.
[http://dx.doi.org/10.1128/AAC.00343-16] [PMID: 27001816]
[72]
Faúndez, M.; Pino, L.; Letelier, P.; Ortiz, C.; López, R.; Seguel, C.; Ferreira, J.; Pavani, M.; Morello, A.; Maya, J.D. Buthionine sulfoximine increases the toxicity of nifurtimox and benznidazole to Trypanosoma cruzi. Antimicrob. Agents Chemother., 2005, 49(1), 126-130.
[http://dx.doi.org/10.1128/AAC.49.1.126-130.2005] [PMID: 15616285]
[73]
Faúndez, M.; López-Muñoz, R.; Torres, G.; Morello, A.; Ferreira, J.; Kemmerling, U.; Orellana, M.; Maya, J.D. Buthionine sulfoximine has anti-Trypanosoma cruzi activity in a murine model of acute Chagas’ disease and enhances the efficacy of nifurtimox. Antimicrob. Agents Chemother., 2008, 52(5), 1837-1839.
[http://dx.doi.org/10.1128/AAC.01454-07] [PMID: 18332173]
[74]
Cencig, S.; Coltel, N.; Truyens, C.; Carlier, Y. Evaluation of benznidazole treatment combined with nifurtimox, posaconazole or AmBisome® in mice infected with Trypanosoma cruzi strains. Int. J. Antimicrob. Agents, 2012, 40(6), 527-532.
[http://dx.doi.org/10.1016/j.ijantimicag.2012.08.002] [PMID: 23063742]
[75]
Kuehn, C.C.; Rodrigues Oliveira, L.G.; Santos, C.D.; Ferreira, D.S.; Alonso Toldo, M.P.; de Albuquerque, S.; do Prado, J.C., Jr Melatonin and dehydroepiandrosterone combination: does this treatment exert a synergistic effect during experimental Trypanosoma cruzi infection? J. Pineal Res., 2009, 47(3), 253-259.
[http://dx.doi.org/10.1111/j.1600-079X.2009.00708.x] [PMID: 19732300]
[76]
Oliveira, L.G.R.; Kuehn, C.C.; Santos, C.D.; Toldo, M.P.A.; do Prado, J.C. Jr Enhanced protection by melatonin and meloxicam combination in experimental infection by Trypanosoma cruzi. Parasite Immunol., 2010, 32(4), 245-251.
[http://dx.doi.org/10.1111/j.1365-3024.2009.01185.x] [PMID: 20398224]
[77]
Fieck, A.; Hurwitz, I.; Kang, A.S.; Durvasula, R. Trypanosoma cruzi: synergistic cytotoxicity of multiple amphipathic anti-microbial peptides to T. cruzi and potential bacterial hosts. Exp. Parasitol., 2010, 125(4), 342-347.
[http://dx.doi.org/10.1016/j.exppara.2010.02.016] [PMID: 20206169]
[78]
Veiga-Santos, P.; Li, K.; Lameira, L.; de Carvalho, T.M.; Huang, G.; Galizzi, M.; Shang, N.; Li, Q.; Gonzalez-Pacanowska, D.; Hernandez-Rodriguez, V.; Benaim, G.; Guo, R.T.; Urbina, J.A.; Docampo, R.; de Souza, W.; Oldfield, E. SQ109, a new drug lead for Chagas disease. Antimicrob. Agents Chemother., 2015, 59(4), 1950-1961.
[http://dx.doi.org/10.1128/AAC.03972-14] [PMID: 25583723]
[79]
Morillo, C.A.; Waskin, H.; Sosa-Estani, S.; Del Carmen Bangher, M.; Cuneo, C.; Milesi, R.; Mallagray, M.; Apt, W.; Beloscar, J.; Gascon, J.; Molina, I.; Echeverria, L.E.; Colombo, H.; Perez-Molina, J.A.; Wyss, F.; Meeks, B.; Bonilla, L.R.; Gao, P.; Wei, B.; McCarthy, M.; Yusuf, S. STOP-CHAGAS Investigators. Benznidazole and posaconazole in eliminating parasites in asymptomatic T. cruzi carriers. J. Am. Coll. Cardiol., 2017, 69(8), 939-947.
[http://dx.doi.org/10.1016/j.jacc.2016.12.023] [PMID: 28231946]

Rights & Permissions Print Cite
Article Metrics
40
3
© 2024 Bentham Science Publishers | Privacy Policy