Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

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

Review Article

Recent Advances in the Development of Broad-Spectrum Antiprotozoal Agents

Author(s): Antonio Moreno-Herrera, Sandra Cortez-Maya, Virgilio Bocanegra-Garcia, Bimal Krishna Banik and Gildardo Rivera*

Volume 28 , Issue 3 , 2021

Published on: 03 March, 2020

Page: [583 - 606] Pages: 24

DOI: 10.2174/0929867327666200303170000

Price: $65

Abstract

Infections caused by Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., Entamoeba histolytica, Giardia lamblia, Plasmodium spp., and Trichomonas vaginalis, are part of a large list of human parasitic diseases. Together, they cause more than 500 million infections per year. These protozoa parasites affect both low- and high-income countries and their pharmacological treatments are limited. Therefore, new and more effective drugs in preclinical development could improve overall therapy for parasitic infections even when their mechanisms of action are unknown. In this review, a number of heterocyclic compounds (diamidine, guanidine, quinoline, benzimidazole, thiazole, diazanaphthalene, and their derivatives) reported as antiprotozoal agents are discussed as options for developing new pharmacological treatments for parasitic diseases.

Keywords: Antiprotozoal, drugs, Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., Giardia lamblia, Trichomonas vaginalis, Plasmodium spp., Entamoeba histolytica.

[1]
Burgess, S.L.; Gilchrist, C.A.; Lynn, T.C.; Petri, W.A. Jr. Parasitic protozoa and interactions with the host intestinal microbiota. Infect. Immun., 2017, 85(8), e00101-e00117.
[http://dx.doi.org/10.1128/IAI.00101-17] [PMID: 28584161]
[2]
Cable, J.; Barber, I.; Boag, B.; Ellison, A.R.; Morgan, E.R.; Murray, K.; Pascoe, E.L.; Sait, S.M.; Wilson, A.J.; Booth, M. Global change, parasite transmission and disease control: lessons from ecology. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2017, 372(1719), 372.
[http://dx.doi.org/10.1098/rstb.2016.0088] [PMID: 28289256]
[3]
Theel, E.S.; Pritt, B.S. Parasites. Microbiol. Spectr., 2016, 4(4)
[http://dx.doi.org/10.1128/microbiolspec.DMIH2-0013-2015] [PMID: 27726821]
[4]
World Health Organization. Neglected tropical diseases, 2020. Available at: http://www.who.int/neglected_ diseases/diseases/en/
[5]
World Health Organization. Guidelines for the treatment of malaria. 3rd ed, 2015. Available at: https://www.who.int/docs/default-source/documents/publications/gmp/guide-lines-for-the-treatment-of-malaria-eng.pdf (Accessed: Jun 12 2018)
[6]
Matuschewski, K. Vaccines against malaria-still a long way to go. FEBS J., 2017, 284(16), 2560-2568.
[http://dx.doi.org/10.1111/febs.14107] [PMID: 28500775]
[7]
Bern, C.; Montgomery, S.P.; Herwaldt, B.L.; Rassi, A., Jr; Marin-Neto, J.A.; Dantas, R.O.; Maguire, J.H.; Acquatella, H.; Morillo, C.; Kirchhoff, L.V.; Gilman, R.H.; Reyes, P.A.; Salvatella, R.; Moore, A.C. Evaluation and treatment of chagas disease in the United States: a systematic review. JAMA, 2007, 298(18), 2171-2181.
[http://dx.doi.org/10.1001/jama.298.18.2171] [PMID: 18000201]
[8]
Bern, C. Chagas’ Disease. N. Engl. J. Med., 2015, 373(19), 1882.
[http://dx.doi.org/10.1056/nejmc1510996] [PMID: 26535522]
[9]
Ponte-Sucre, A. Propiedades químicas estructurales de compuestos que actúan contra el Trypanosoma brucei (Revisión). VITAE, 2015, 62, 1-9.
[10]
Soto, J.; Soto, P. Miltefosina oral para el tratamiento de la leishmaniasis. Biomedica, 2006, 26(Suppl. 1), 207-217.
[http://dx.doi.org/10.7705/biomedica.v26i1.1514] [PMID: 17361856]
[11]
Gonzales, M.L.; Dans, L.F.; Martinez, E.G. Antiamoebic drugs for treating amoebic colitis. Cochrane Database Syst. Rev., 2009, 2(2)CD006085
[http://dx.doi.org/10.1002/14651858.cd006085.pub2] [PMID: 19370624]
[12]
Chacín-Bonilla, L. Farmacoterapia actual de la amibiasis, avances en nuevas drogas y diseño de una vacuna. Invest. Clin., 2012, 53(3), 301-314.
[PMID: 23248973]
[13]
Granados, C.E.; Reveiz, L.; Uribe, L.G.; Criollo, C.P. Drugs for treating giardiasis. Cochrane Database Syst. Rev., 2012, 12(12)CD007787
[http://dx.doi.org/10.1002/14651858.CD007787.pub2] [PMID: 23235648]
[14]
Escobedo, A.A.; Almirall, P.; Cimerman, S.; Lalle, M.; Pacheco, F.; Acanda, C.Z.; Sánchez, N. Chloroquine: an old drug with new perspective against giardiasis. Recent Pat. Antiinfect. Drug Discov, 2015, 10(2), 134-141.
[http://dx.doi.org/10.2174/1574891X10666150914122118] [PMID: 26365362]
[15]
Mahdi, N.K.; Gany, Z.H.; Sharief, M. Alternative drugs against Trichomonas vaginalis. East. Mediterr. Health J., 2006, 12(5), 679-684.
[PMID: 17333809]
[16]
Sharma, R.S.; Mathur, A.K.; Chandhiok, N.; Datey, S.; Saxena, N.C.; Gopalan, S.; Sharma, S.; Mittal, S.; Sehgal, R.; Sumandal, B.K.; Chanda, A.; Salvi, V.; Mutalik, N.; Coyaji, K.J.; Gibsson, A.; Hazari, K.; Kalgutkar, S.
Talwar, G.P. Phase II clinical trial with Praneem polyherbal tablets for assessment of their efficacy in symptomatic women with abnormal vaginal discharge (an ICMR task force study). Trans. R. Soc. Trop. Med. Hyg., 2009, 103(2), 167-172.
[http://dx.doi.org/10.1016/j.trstmh.2008.09.012] [PMID: 18990416]
[17]
Vieira, P. B.; Giordani, R.B.; Macedo, A.J.; Tasca, T. Natural and synthetic compound anti-Trichomonas vaginalis: an update review. Parasitol. Res., 2015, 114(4), 1249-1261.
[http://dx.doi.org/10.1007/s00436-015-4340-3] [PMID: 25786392]
[18]
Büscher, P.; Cecchi, G.; Jamonneau, V.; Priotto, G. Human African trypanosomiasis. Lancet, 2017, 390(10110), 2397-2409.
[http://dx.doi.org/10.1016/S0140-6736(17)31510-6] [PMID: 28673422]
[19]
Cullen, D.R.; Mocerino, M. A brief review of drug discovery research for human African trypanosomiasis. Curr. Med. Chem., 2017, 24(7), 701-717.
[http://dx.doi.org/10.2174/0929867324666170120160034] [PMID: 28117003]
[20]
Pérez-Molina, J.A.; Molina, I. Chagas disease. Lancet, 2018, 391(10115), 82-94.
[http://dx.doi.org/10.1016/S0140-6736(17)31612-4] [PMID: 28673423]
[21]
Torres-Guerrero, E.; Quintanilla-Cedillo, M.R.; Ruiz-Esmenjaud, J.; Arenas, R. Leishmaniasis: a review. F1000 Res., 2017, 6, 750.
[http://dx.doi.org/10.12688/f1000research.11120.1] [PMID: 28649370]
[22]
Prakash, V.; Bhimji, S. Abscess, Amebic Liver. StatPearls. 2017. Available at: https://www.ncbi.nlm.nih.gov/books/NBK430832/
[23]
Adam, E.A.; Yoder, J.S.; Gould, L.H.; Hlavsa, M.C.; Gargano, J.W. Giardiasis outbreaks in the United States, 1971-2011. Epidemiol. Infect., 2016, 144(13), 2790-2801.
[http://dx.doi.org/10.1017/S0950268815003040] [PMID: 26750152]
[24]
Koehler, A.V.; Jex, A.R.; Haydon, S.R.; Stevens, M.A.; Gasser, R.B. Giardia/giardiasis - a perspective on diagnostic and analytical tools. Biotechnol. Adv., 2014, 32(2), 280-289.
[http://dx.doi.org/10.1016/j.biotechadv.2013.10.009] [PMID: 24189092]
[25]
Phillips, M.A.; Burrows, J.N.; Manyando, C.; van Huijsduijnen, R.H.; Van Voorhis, W.C.; Wells, T.N.C. Malaria. Nat. Rev. Dis. Primers, 2017, 3, 17050.
[http://dx.doi.org/10.1038/nrdp.2017.50] [PMID: 28770814]
[26]
Menezes, C.B.; Frasson, A.P.; Tasca, T. Trichomoniasis - are we giving the deserved attention to the most common non-viral sexually transmitted disease worldwide? Microb. Cell, 2016, 3(9), 404-419.
[http://dx.doi.org/10.15698/mic2016.09.526] [PMID: 28357378]
[27]
de Brum Vieira, P.; Tasca, T.; Secor, W.E. Challenges and persistent questions in the treatment of trichomoniasis. Curr. Top. Med. Chem., 2017, 17(11), 1249-1265.
[http://dx.doi.org/10.2174/1568026616666160930150429] [PMID: 27697044]
[28]
The TDR Targets Database. Leverage diverse datasets to facilitate drug discovery for neglected disease pathgens., Available at: http://tdrtargets.org
[29]
Francesconi, I.; Wilson, W.D.; Tanious, F.A.; Hall, J.E.; Bender, B.C.; Tidwell, R.R.; McCurdy, D.; Boykin, D.W. 2,4-Diphenyl furan diamidines as novel anti-Pneumocystis carinii pneumonia agents. J. Med. Chem., 1999, 42(12), 2260-2265.
[http://dx.doi.org/10.1021/jm990071c] [PMID: 10377232]
[30]
Bailly, C.; Dassonneville, L.; Carrasco, C.; Lucas, D.; Kumar, A.; Boykin, D.W.; Wilson, W.D. Relationships between topoisomerase II inhibition, sequence-specificity and DNA binding mode of dicationic diphenylfuran derivatives. Anticancer Drug Des., 1999, 14(1), 47-60.
[PMID: 10363027]
[31]
Dardonville, C. Recent advances in antitrypanosomal chemotherapy: patent literature 2002-2005. Expert Opin. Ther. Pat., 2005, 15, 1241-1257.
[http://dx.doi.org/10.1517/13543776.15.9.1241]
[32]
Brun, R.; Blum, J.; Chappuis, F.; Burri, C. Human African trypanosomiasis. Lancet, 2010, 375(9709), 148-159.
[http://dx.doi.org/10.1016/S0140-6736(09)60829-1] [PMID: 19833383]
[33]
Wenzler, T.; Boykin, D.W.; Ismail, M.A.; Hall, J.E.; Tidwell, R.R.; Brun, R. New treatment option for second-stage African sleeping sickness: in vitro and in vivo efficacy of aza analogs of DB289. Antimicrob. Agents Chemother., 2009, 53(10), 4185-4192.
[http://dx.doi.org/10.1128/AAC.00225-09] [PMID: 19620327]
[34]
Paine, M.F.; Wang, M.Z.; Generaux, C.N.; Boykin, D.W.; Wilson, W.D.; De Koning, H.P.; Olson, C.A.; Pohlig, G.; Burri, C.; Brun, R.; Murilla, G.A.; Thuita, J.K.; Barrett, M.P.; Tidwell, R.R. Diamidines for human African trypanosomiasis. Curr. Opin. Investig. Drugs, 2010, 11(8), 876-883.
[PMID: 20721830]
[35]
Kumar, A.; Boykin, D.; Wilson, W.; Jones, S.; Bender, B.; Dykstra, C.; Hall, J.; Tidwell, R. Anti-Pneumocystis carinii pneumonia activity of dicationic 2,4-diarylpyrimidines. Eur. J. Med. Chem., 1996, 31(10), 767-773.
[http://dx.doi.org/10.1016/0223-5234(96)83970-5] [PMID: 22026932]
[36]
Boykin, D.; Kumar, A.; Bajic, M.; Wilson, W.; Bender, B.; Hall, J.; Tidwell, R. Anti-Pneumocystis carinii pneumonia activity of dicationic diaryl methylprimidines. Eur. J. Med. Chem., 1998, 32(12), 965-972.
[http://dx.doi.org/10.1016/S0223-5234(97)89640-7]
[37]
Branowska, D.; Farahat, A.A.; Kumar, A.; Wenzler, T.; Brun, R.; Liu, Y.; Wilson, W.D.; Boykin, D.W. Synthesis and antiprotozoal activity of 2,5-bis[amidinoaryl]thiazoles. Bioorg. Med. Chem., 2010, 18(10), 3551-3558.
[http://dx.doi.org/10.1016/j.bmc.2010.03.058] [PMID: 20403703]
[38]
Ismail, M.A.; Bialy, S.A.; Brun, R.; Wenzler, T.; Nanjunda, R.; Wilson, W.D.; Boykin, D.W. Dicationic phenyl-2,2′-bichalcophenes and analogues as antiprotozoal agents. Bioorg. Med. Chem., 2011, 19(2), 978-984.
[http://dx.doi.org/10.1016/j.bmc.2010.11.047] [PMID: 21194955]
[39]
Nguyen, N.; Boykin, D.W.; Wilson, W.D. DNA minor groove interactions of antiparasitic diamidines: reevaluation of the crescent-shape concept in groove-binding; Synthetic and Biophysical Studies of DNA Binding Compounds, 2007, pp. 39-66.
[40]
Ismail, M.A.; Arafa, R.K.; Wenzler, T.; Brun, R.; Tanious, F.A.; Wilson, W.D.; Boykin, D.W. Synthesis and antiprotozoal activity of novel bis-benzamidino imidazo[1,2-a]pyridines and 5,6,7,8-tetrahydro-imidazo[1,2-a]pyridines. Bioorg. Med. Chem., 2008, 16(2), 683-691.
[http://dx.doi.org/10.1016/j.bmc.2007.10.042] [PMID: 17976993]
[41]
Hu, L.; Arafa, R.K.; Ismail, M.A.; Patel, A.; Munde, M.; Wilson, W.D.; Wenzler, T.; Brun, R.; Boykin, D.W. Synthesis and activity of azaterphenyl diamidines against Trypanosoma brucei rhodesiense and Plasmodium falciparum. Bioorg. Med. Chem., 2009, 17(18), 6651-6658.
[http://dx.doi.org/10.1016/j.bmc.2009.07.080] [PMID: 19699098]
[42]
Hu, L.; Patel, A.; Bondada, L.; Yang, S.; Wang, M.Z.; Munde, M.; Wilson, W.D.; Wenzler, T.; Brun, R.; Boykin, D.W. Synthesis and antiprotozoal activity of dicationic 2,6-diphenylpyrazines and aza-analogues. Bioorg. Med. Chem., 2013, 21(21), 6732-6741.
[http://dx.doi.org/10.1016/j.bmc.2013.08.006] [PMID: 24012380]
[43]
Giordani, R.B.; Araújo, D.P.; Duarte, M.; Zuanazzi, J.A.; Tasca, T.; De Almeida, M.V. Anti-protozoal activity of diamine derivatives. Biomed. Pharmacother., 2011, 65(1), 60-62.
[http://dx.doi.org/10.1016/j.biopha.2010.10.006] [PMID: 21186095]
[44]
Rodríguez, F.; Rozas, I.; Kaiser, M.; Brun, R.; Nguyen, B.; Wilson, W.D.; García, R.N.; Dardonville, C. New bis(2-aminoimidazoline) and bisguanidine DNA minor groove binders with potent in vivo antitrypanosomal and antiplasmodial activity. J. Med. Chem., 2008, 51(4), 909-923.
[http://dx.doi.org/10.1021/jm7013088] [PMID: 18247550]
[45]
Dardonville, C.; Barrett, M.P.; Brun, R.; Kaiser, M.; Tanious, F.; Wilson, W.D. DNA binding affinity of bisguanidine and bis(2-aminoimidazoline) derivatives with in vivo antitrypanosomal activity. J. Med. Chem., 2006, 49(12), 3748-3752.
[http://dx.doi.org/10.1021/jm060295c] [PMID: 16759117]
[46]
Dardonville, C.; Brun, R. Bisguanidine, bis(2-amino-imidazoline), and polyamine derivatives as potent and selective chemotherapeutic agents against Trypanosoma brucei rhodesiense. Synthesis and in vitro evaluation. J. Med. Chem., 2004, 47(9), 2296-2307.
[http://dx.doi.org/10.1021/jm031024u] [PMID: 15084128]
[47]
Arafa, R.K.; Brun, R.; Wenzler, T.; Tanious, F.A.; Wilson, W.D.; Stephens, C.E.; Boykin, D.W. Synthesis, DNA affinity, and antiprotozoal activity of fused ring dicationic compounds and their prodrugs. J. Med. Chem., 2005, 48(17), 5480-5488.
[http://dx.doi.org/10.1021/jm058190h] [PMID: 16107146]
[48]
Ríos Martínez, C.H.; Lagartera, L.; Kaiser, M.; Dardonville, C. Antiprotozoal activity and DNA binding of N-substituted N-phenylbenzamide and 1,3-diphenylurea bisguanidines. Eur. J. Med. Chem., 2014, 81, 481-491.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.083] [PMID: 24865793]
[49]
Stephens, C.E.; Brun, R.; Salem, M.M.; Werbovetz, K.A.; Tanious, F.; Wilson, W.D.; Boykin, D.W. The activity of diguanidino and ‘reversed’ diamidino 2,5-diarylfurans versus Trypanosoma cruzi and Leishmania donovani. Bioorg. Med. Chem. Lett., 2003, 13(12), 2065-2069.
[http://dx.doi.org/10.1016/S0960-894X(03)00319-6] [PMID: 12781196]
[50]
Arafa, R.K.; Brun, R.; Werbovetz, K.A.; Tanious, F.A.; David Wilson, W.; Boykin, D.W. Synthesis of dicationic 2,5-diarylpyrroles. Heterocycl. Commun., 2004, 10, 423-428.
[http://dx.doi.org/10.1515/HC.2004.10.6.423]
[51]
Arafa, R.K.; Ismail, M.A.; Munde, M.; Wilson, W.D.; Wenzler, T.; Brun, R.; Boykin, D.W. Novel linear triaryl guanidines, N-substituted guanidines and potential prodrugs as antiprotozoal agents. Eur. J. Med. Chem., 2008, 43(12), 2901-2908.
[http://dx.doi.org/10.1016/j.ejmech.2008.02.008] [PMID: 18455271]
[52]
Patrick, D.A.; Ismail, M.A.; Arafa, R.K.; Wenzler, T.; Zhu, X.; Pandharkar, T.; Jones, S.K.; Werbovetz, K.A.; Brun, R.; Boykin, D.W.; Tidwell, R.R. Synthesis and antiprotozoal activity of dicationic m-terphenyl and 1,3-dipyridylbenzene derivatives. J. Med. Chem., 2013, 56(13), 5473-5494.
[http://dx.doi.org/10.1021/jm400508e] [PMID: 23795673]
[53]
Arafa, R.K.; Wenzler, T.; Brun, R.; Chai, Y.; Wilson, W.D. Molecular modeling study and synthesis of novel dicationic flexible triaryl guanidines and imidamides as antiprotozoal agents. Eur. J. Med. Chem., 2011, 46(12), 5852-5860.
[http://dx.doi.org/10.1016/j.ejmech.2011.09.047] [PMID: 22005186]
[54]
Ekoue-Kovi, K.; Yearick, K.; Iwaniuk, D.P.; Natarajan, J.K.; Alumasa, J.; de Dios, A.C.; Roepe, P.D.; Wolf, C. Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas. Bioorg. Med. Chem., 2009, 17(1), 270-283.
[http://dx.doi.org/10.1016/j.bmc.2008.11.009] [PMID: 19041248]
[55]
Kumar, A.; Srivastava, K.; Raja Kumar, S.; Puri, S.K.; Chauhan, P.M.S. Synthesis and bioevaluation of hybrid 4-aminoquinoline triazines as a new class of antimalarial agents. Bioorg. Med. Chem. Lett., 2008, 18(24), 6530-6533.
[http://dx.doi.org/10.1016/j.bmcl.2008.10.049] [PMID: 18951791]
[56]
Nava-Zuazo, C.; Estrada-Soto, S.; Guerrero-Alvarez, J.; León-Rivera, I.; Molina-Salinas, G.M.; Said-Fernández, S.; Chan-Bacab, M.J.; Cedillo-Rivera, R.; Moo-Puc, R.; Mirón-López, G.; Navarrete-Vazquez, G. Design, synthesis, and in vitro antiprotozoal, antimycobacterial activities of N-2-[(7-chloroquinolin-4-yl)amino]ethylureas. Bioorg. Med. Chem., 2010, 18(17), 6398-6403.
[http://dx.doi.org/10.1016/j.bmc.2010.07.008] [PMID: 20674375]
[57]
Domínguez, J.N. Chemotherapeutic agents against malaria: what next after chloroquine? Curr. Top. Med. Chem., 2002, 2(11), 1173-1185.
[http://dx.doi.org/10.2174/1568026023392986] [PMID: 12171580]
[58]
de Souza, M.V.; Pais, K.C.; Kaiser, C.R.; Peralta, M.A. de L Ferreira, M.; Lourenço, M.C. Synthesis and in vitro antitubercular activity of a series of quinoline derivatives. Bioorg. Med. Chem., 2009, 17(4), 1474-1480.
[http://dx.doi.org/10.1016/j.bmc.2009.01.013] [PMID: 19188070]
[59]
Candéa, A.L. Ferreira, Mde.L.; Pais, K.C.; Cardoso, L.N.; Kaiser, C.R.; Henriques, Md.; Lourenço, M.C.; Bezerra, F.A.; de Souza, M.V. Synthesis and antitubercular activity of 7-chloro-4-quinolinylhydrazones derivatives. Bioorg. Med. Chem. Lett., 2009, 19(22), 6272-6274.
[http://dx.doi.org/10.1016/j.bmcl.2009.09.098] [PMID: 19819134]
[60]
Vale, N.; Moreira, R.; Gomes, P. Primaquine revisited six decades after its discovery. Eur. J. Med. Chem., 2009, 44(3), 937-953.
[http://dx.doi.org/10.1016/j.ejmech.2008.08.011] [PMID: 18930565]
[61]
Hill, D.R.; Baird, J.K.; Parise, M.E.; Lewis, L.S.; Ryan, E.T.; Magill, A.J. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am. J. Trop. Med. Hyg., 2006, 75(3), 402-415.
[http://dx.doi.org/10.4269/ajtmh.2006.75.402] [PMID: 16968913]
[62]
Constantino, L.; Paixão, P.; Moreira, R.; Portela, M.J.; Do Rosario, V.E.; Iley, J. Metabolism of primaquine by liver homogenate fractions. Evidence for monoamine oxidase and cytochrome P450 involvement in the oxidative deamination of primaquine to carboxyprimaquine. Exp. Toxicol. Pathol., 1999, 51(4-5), 299-303.
[http://dx.doi.org/10.1016/S0940-2993(99)80010-4] [PMID: 10445386]
[63]
Kaur, K.; Patel, S.R.; Patil, P.; Jain, M.; Khan, S.I.; Jacob, M.R.; Tekwani, B.L.; Jain, R. Synthesis, antimalarial, antileishmanial, antimicrobial, cytotoxicity, and methemoglobin (MetHB) formation activities of new 8-quinolinamines. Bioorg. Med. Chem., 2007, 15(2), 915-930.
[http://dx.doi.org/10.1016/j.bmc.2006.10.036] [PMID: 17084633]
[64]
Kaur, K.; Jain, M.; Khan, S.I.; Jacob, M.R.; Tekwani, B.L.; Singh, S.; Singh, P.P.; Jain, R. Synthesis, antiprotozoal, antimicrobial, β-hematin inhibition, cytotoxicity and methemoglobin (MetHb) formation activities of bis(8-amino-quinolines). Bioorg. Med. Chem., 2011, 19(1), 197-210.
[http://dx.doi.org/10.1016/j.bmc.2010.11.036] [PMID: 21172735]
[65]
Araújo, N.C.; Barton, V.; Jones, M.; Stocks, P.A.; Ward, S.A.; Davies, J.; Bray, P.G.; Shone, A.E.; Cristiano, M.L.; O’Neill, P.M. Semi-synthetic and synthetic 1,2,4-trioxaquines and 1,2,4-trioxolaquines: synthesis, preliminary SAR and comparison with acridine endoperoxide conjugates. Bioorg. Med. Chem. Lett., 2009, 19(7), 2038-2043.
[http://dx.doi.org/10.1016/j.bmcl.2009.02.013] [PMID: 19251414]
[66]
Salahuddin, A.; Inam, A.; van Zyl, R.L.; Heslop, D.C.; Chen, C.T.; Avecilla, F.; Agarwal, S.M.; Azam, A. Synthesis and evaluation of 7-chloro-4-(piperazin-1-yl)quinoline-sulfonamide as hybrid antiprotozoal agents. Bioorg. Med. Chem., 2013, 21(11), 3080-3089.
[http://dx.doi.org/10.1016/j.bmc.2013.03.052] [PMID: 23602620]
[67]
Hong, Y.L.; Hossler, P.A.; Calhoun, D.H.; Meshnick, S.R. Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. Antimicrob. Agents Chemother., 1995, 39(8), 1756-1763.
[http://dx.doi.org/10.1128/AAC.39.8.1756] [PMID: 7486915]
[68]
Tekwani, B.L.; Walker, L.A. Targeting the hemozoin synthesis pathway for new antimalarial drug discovery: technologies for in vitro beta-hematin formation assay. Comb. Chem. High Throughput Screen., 2005, 8(1), 63-79.
[http://dx.doi.org/10.2174/1386207053328101] [PMID: 15720198]
[69]
Ansari, M.F.; Hayat, F.; Inam, A.; Kathrada, F.; van Zyl, R.L.; Coetzee, M.; Ahmad, K.; Shin, D.; Azam, A. New antiprotozoal agents: synthesis and biological evaluation of different 4-(7-chloroquinolin-4-yl) piperazin-1-yl) pyrrolidin-2-yl)methanone derivatives. Bioorg. Med. Chem. Lett., 2017, 27(3), 460-465.
[http://dx.doi.org/10.1016/j.bmcl.2016.12.043] [PMID: 28027871]
[70]
Inam, A.; Van Zyl, R.L.; van Vuuren, N.J.; Chen, C.T.; Avecilla, F.; Agarwal, S.M.; Azam, A. Chloroquinoline-acetamide hybrids: a promising series of potential antiprotozoal agents. RSC Advances, 2015, 5(60), 48368-48381.
[http://dx.doi.org/10.1039/C5RA05472A]
[71]
Leeza Zaidi, S.; Mittal, S.; Rajala, M.S.; Avecilla, F.; Husain, M.; Azam, A. Synthesis, characterization and antiamoebic activity of chalcones bearing N-substituted ethanamine tail. Eur. J. Med. Chem., 2015, 98, 179-189.
[http://dx.doi.org/10.1016/j.ejmech.2015.05.013] [PMID: 26021707]
[72]
Zhao, Y.; Shadrick, W.R.; Wallace, M.J.; Wu, Y.; Griffith, E.C.; Qi, J.; Yun, M.K.; White, S.W.; Lee, R.E. Pterin-sulfa conjugates as dihydropteroate synthase inhibitors and antibacterial agents. Bioorg. Med. Chem. Lett., 2016, 26(16), 3950-3954.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.006] [PMID: 27423480]
[73]
Upadhayaya, R.S.; Dixit, S.S.; Földesi, A.; Chattopadhyaya, J. New antiprotozoal agents: their synthesis and biological evaluations. Bioorg. Med. Chem. Lett., 2013, 23(9), 2750-2758.
[http://dx.doi.org/10.1016/j.bmcl.2013.02.054] [PMID: 23518280]
[74]
Garcia, S.; Ramos, C.O.; Senra, J.F.; Vilas-Boas, F.; Rodrigues, M.M.; Campos-de-Carvalho, A.C.; Ribeiro-Dos-Santos, R.; Soares, M.B. Treatment with benznidazole during the chronic phase of experimental Chagas’ disease decreases cardiac alterations. Antimicrob. Agents Chemother., 2005, 49(4), 1521-1528.
[http://dx.doi.org/10.1128/AAC.49.4.1521-1528.2005] [PMID: 15793134]
[75]
Rivarola, H.W.; Paglini-Oliva, P.A. Trypanosoma cruzi trypanothione reductase inhibitors: phenothiazines and related compounds modify experimental Chagas’ disease evolution. Curr. Drug Targets Cardiovasc. Haematol. Disord., 2002, 2(1), 43-52.
[http://dx.doi.org/10.2174/1568006023337745] [PMID: 12769656]
[76]
Paila, Y.D.; Saha, B.; Chattopadhyay, A. Amphotericin B inhibits entry of Leishmania donovani into primary macrophages. Biochem. Biophys. Res. Commun., 2010, 399(3), 429-433.
[http://dx.doi.org/10.1016/j.bbrc.2010.07.099] [PMID: 20678487]
[77]
Gros, L.; Castillo-Acosta, V.M.; Jiménez Jiménez, C.; Sealey-Cardona, M.; Vargas, S.; Manuel Estévez, A.; Yardley, V.; Rattray, L.; Croft, S.L.; Ruiz-Perez, L.M.; Urbina, J.A.; Gilbert, I.H.; González-Pacanowska, D. New azasterols against Trypanosoma brucei: role of 24-sterol methyltransferase in inhibitor action. Antimicrob. Agents Chemother., 2006, 50(8), 2595-2601.
[http://dx.doi.org/10.1128/AAC.01508-05] [PMID: 16870747]
[78]
Horton, D.A.; Bourne, G.T.; Smythe, M.L. The combinatorial synthesis of bicyclic privileged structures or privileged substructures. Chem. Rev., 2003, 103(3), 893-930.
[http://dx.doi.org/10.1021/cr020033s] [PMID: 12630855]
[79]
Navarrete-Vázquez, G. Rojano-Vilchis, Mde.M.; Yépez-Mulia, L.; Meléndez, V.; Gerena, L.; Hernández-Campos, A.; Castillo, R.; Hernández-Luis, F. Synthesis and antiprotozoal activity of some 2-(trifluoromethyl)-1H-benzimida-zole bioisosteres. Eur. J. Med. Chem., 2006, 41(1), 135-141.
[http://dx.doi.org/10.1016/j.ejmech.2005.09.001] [PMID: 16260067]
[80]
Torres-Gómez, H.; Hernández-Núñez, E.; León-Rivera, I.; Guerrero-Alvarez, J.; Cedillo-Rivera, R.; Moo-Puc, R.; Argotte-Ramos, R. Rodríguez-Gutiérrez, Mdel.C.; Chan-Bacab, M.J.; Navarrete-Vázquez, G. Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids. Bioorg. Med. Chem. Lett., 2008, 18(11), 3147-3151.
[http://dx.doi.org/10.1016/j.bmcl.2008.05.009] [PMID: 18486471]
[81]
Valdez, J.; Cedillo, R.; Hernández-Campos, A.; Yépez, L.; Hernández-Luis, F.; Navarrete-Vázquez, G.; Tapia, A.; Cortés, R.; Hernández, M.; Castillo, R. Synthesis and antiparasitic activity of 1H-benzimidazole derivatives. Bioorg. Med. Chem. Lett., 2002, 12(16), 2221-2224.
[http://dx.doi.org/10.1016/S0960-894X(02)00346-3] [PMID: 12127542]
[82]
Valdez-Padilla, D.; Rodríguez-Morales, S.; Hernández-Campos, A.; Hernández-Luis, F.; Yépez-Mulia, L.; Tapia-Contreras, A.; Castillo, R. Synthesis and antiprotozoal activity of novel 1-methylbenzimidazole derivatives. Bioorg. Med. Chem., 2009, 17(4), 1724-1730.
[http://dx.doi.org/10.1016/j.bmc.2008.12.059] [PMID: 19186059]
[83]
Hernández-Covarrubias, C.; Vilchis-Reyes, M.A.; Yépez-Mulia, L.; Sánchez-Díaz, R.; Navarrete-Vázquez, G.; Hernández-Campos, A.; Castillo, R.; Hernández-Luis, F. Exploring the interplay of physicochemical properties, membrane permeability and giardicidal activity of some benzimidazole derivatives. Eur. J. Med. Chem., 2012, 52, 193-204.
[http://dx.doi.org/10.1016/j.ejmech.2012.03.014] [PMID: 22464423]
[84]
Hernández-Luis, F.; Hernández-Campos, A.; Castillo, R.; Navarrete-Vázquez, G.; Soria-Arteche, O.; Hernández-Hernández, M.; Yépez-Mulia, L. Synthesis and biological activity of 2-(trifluoromethyl)-1H-benzimidazole derivatives against some protozoa and Trichinella spiralis. Eur. J. Med. Chem., 2010, 45(7), 3135-3141.
[http://dx.doi.org/10.1016/j.ejmech.2010.03.050] [PMID: 20430484]
[85]
Soria-Arteche, O.; Hernández-Campos, A.; Yépez-Mulia, L.; Trejo-Soto, P.J.; Hernández-Luis, F.; Gres-Molina, J.; Maldonado, L.A.; Castillo, R. Synthesis and antiprotozoal activity of nitazoxanide-N-methylbenzimidazole hybrids. Bioorg. Med. Chem. Lett., 2013, 23(24), 6838-6841.
[http://dx.doi.org/10.1016/j.bmcl.2013.10.011] [PMID: 24183540]
[86]
Karaaslan, C.; Kaiser, M.; Brun, R.; Göker, H. Synthesis and potent antiprotozoal activity of mono/di amidino 2-anilinobenzimidazoles versus Plasmodium falciparum and Trypanosoma brucei rhodesiense. Bioorg. Med. Chem., 2016, 24(18), 4038-4044.
[http://dx.doi.org/10.1016/j.bmc.2016.06.047] [PMID: 27387356]
[87]
Ismail, M.A.; Batista-Parra, A.; Miao, Y.; Wilson, W.D.; Wenzler, T.; Brun, R.; Boykin, D.W. Dicationic near-linear biphenyl benzimidazole derivatives as DNA-targeted antiprotozoal agents. Bioorg. Med. Chem., 2005, 13(24), 6718-6726.
[http://dx.doi.org/10.1016/j.bmc.2005.07.024] [PMID: 16099661]
[88]
Siddiqui, N.; Arshad, M.F.; Ahsan, W.; Alam, M.S. Thiazoles: a valuable insight into the recent advances and biological activities. Int. J. Pharm. Sci. Drug Res., 2009, 1(3), 136-143.
[89]
Das, J.; Chen, P.; Norris, D.; Padmanabha, R.; Lin, J.; Moquin, R.V.; Shen, Z.; Cook, L.S.; Doweyko, A.M.; Pitt, S.; Pang, S.; Shen, D.R.; Fang, Q.; de Fex, H.F.; McIntyre, K.W.; Shuster, D.J.; Gillooly, K.M.; Behnia, K.; Schieven, G.L.; Wityak, J.; Barrish, J.C. 2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinib, BMS-354825) as a potent pan-Src kinase inhibitor. J. Med. Chem., 2006, 49(23), 6819-6832.
[http://dx.doi.org/10.1021/jm060727j] [PMID: 17154512]
[90]
De Souza, M.V.N.; De Almeida, M.V. Drogas anti-VIH: pasado, presente e perspectivas futuras. Quim. Nova, 2003, 26, 366-372.
[http://dx.doi.org/10.1590/S0100-40422003000300014]
[91]
Pasqualotto, A.C.; Thiele, K.O.; Goldani, L.Z. Novel triazole antifungal drugs: focus on isavuconazole, ravuconazole and albaconazole. Curr. Opin. Investig. Drugs, 2010, 11(2), 165-174.
[PMID: 20112166]
[92]
Fox, L.M.; Saravolatz, L.D. Nitazoxanide: a new thiazolide antiparasitic agent. Clin. Infect. Dis., 2005, 40(8), 1173-1180.
[http://dx.doi.org/10.1086/428839] [PMID: 15791519]
[93]
Rehman, M.Z.; Anwar, C.J.; Ahmad, S. An efficient synthesis of 2-Alkyl-4-hydroxy-2H-1,2-benzothiazine-3-carbo-xamide-1,1-dioxides. Bull. Korean Chem. Soc., 2005, 26, 1771-1775.
[http://dx.doi.org/10.5012/bkcs.2005.26.11.1771]
[94]
Knadler, M.P.; Bergstrom, R.F.; Callaghan, J.T.; Rubin, A. Nizatidine, an H2-blocker. Its metabolism and disposition in man. Drug Metab. Dispos., 1986, 14(2), 175-182.
[PMID: 2870891]
[95]
Nauen, R.; Ebbinghaus-Kintscher, U.; Salgado, V.L.; Kaussmann, M. Thiamethoxam is a neonicotinoid precursor converted to clothianidin in insects and plants. Pestic. Biochem. Physiol., 2003, 76(2), 55-69.
[http://dx.doi.org/10.1016/S0048-3575(03)00065-8]
[96]
Rossignol, J.F.; Cavier, R. A new derivative of 2-benzamido 5-nitrothiazoles. Chem. Abstr., 1975, 83, 28216.
[97]
Broekhuysen, J.; Stockis, A.; Lins, R.L.; De Graeve, J.; Rossignol, J.F. Nitazoxanide: pharmacokinetics and metabolism in man. Int. J. Clin. Pharmacol. Ther., 2000, 38(8), 387-394.
[http://dx.doi.org/10.5414/CPP38387] [PMID: 10984012]
[98]
Navarrete-Vazquez, G.; Chávez-Silva, F.; Argotte-Ramos, R. Rodríguez-Gutiérrez, Mdel.C.; Chan-Bacab, M.J.; Cedillo-Rivera, R.; Moo-Puc, R.; Hernández-Nuñez, E. Synthesis of benzologues of nitazoxanide and tizoxanide: a comparative study of their in vitro broad-spectrum antiprotozoal activity. Bioorg. Med. Chem. Lett., 2011, 21(10), 3168-3171.
[http://dx.doi.org/10.1016/j.bmcl.2011.02.100] [PMID: 21397502]
[99]
Goodarzi, M.; da Cunha, E.F.; Freitas, M.P.; Ramalho, T.C. QSAR and docking studies of novel antileishmanial diaryl sulfides and sulfonamides. Eur. J. Med. Chem., 2010, 45(11), 4879-4889.
[http://dx.doi.org/10.1016/j.ejmech.2010.07.060] [PMID: 20728249]
[100]
da Silva, L.E.; de Sousa, P.T.; Jr Maciel, E.N.; Korting-Nunes, R.; Eger, I.; Steindel, M.; Andrade-Rebelo, R. In vitro antiprotozoal evaluation of zinc and copper complexes based on sulfonamides containing 8-aminoquinoline ligands. Lett. Drug Des. Discov., 2010, 7(9), 679-685.
[http://dx.doi.org/10.2174/157018010792929586]
[101]
Khan, K.M.; Khan, M.Z.; Taha, M.; Maharvi, G.M.; Saify, Z.S.; Parveen, S.; Choudhary, M.I. Leishmanicidal potential of N-substituted morpholine derivatives: synthesis and structure-activity relationships. Nat. Prod. Res., 2009, 23(5), 479-484.
[http://dx.doi.org/10.1080/14786410802090359] [PMID: 19296393]
[102]
Altenkämper, M.; Bechem, B.; Perruchon, J.; Heinrich, S.; Mädel, A.; Ortmann, R.; Dahse, H.M.; Freunscht, E.; Wang, Y.; Rath, J.; Stich, A.; Hitzler, M.; Chiba, P.; Lanzer, M.; Schlitzer, M. Antimalarial and antitrypanosomal activity of a series of amide and sulfonamide derivatives of a 2,5-diaminobenzophenone. Bioorg. Med. Chem., 2009, 17(22), 7690-7697.
[http://dx.doi.org/10.1016/j.bmc.2009.09.043] [PMID: 19819706]
[103]
Dea-Ayuela, M.A.; Castillo, E.; González-Álvarez, M.; Vega, C.; Rolón, M.; Bolás-Fernández, F.; Borrás, J.; González-Rosende, M.E. In vivo and in vitro anti-leishmanial activities of 4-nitro-N-pyrimidin- and N-pyrazin-2-ylbenzenesulfonamides, and N2-(4-nitrophenyl)-N1-propylglycinamide. Bioorg. Med. Chem., 2009, 17(21), 7449-7456.
[http://dx.doi.org/10.1016/j.bmc.2009.09.030] [PMID: 19811921]
[104]
Bilbao-Ramos, P.; Galiana-Roselló, C.; Dea-Ayuela, M.A.; González-Alvarez, M.; Vega, C.; Rolón, M.; Pérez-Serrano, J.; Bolás-Fernández, F.; González-Rosende, M.E. Nuclease activity and ultrastructural effects of new sulfonamides with anti-leishmanial and trypanocidal activities. Parasitol. Int., 2012, 61(4), 604-613.
[http://dx.doi.org/10.1016/j.parint.2012.05.015] [PMID: 22668836]
[105]
Nava-Zuazo, C.; Chávez-Silva, F.; Moo-Puc, R.; Chan-Bacab, M.J.; Ortega-Morales, B.O.; Moreno-Díaz, H.; Díaz-Coutiño, D.; Hernández-Núñez, E.; Navarrete-Vázquez, G. 2-acylamino-5-nitro-1,3-thiazoles: preparation and in vitro bioevaluation against four neglected protozoan parasites. Bioorg. Med. Chem., 2014, 22(5), 1626-1633.
[http://dx.doi.org/10.1016/j.bmc.2014.01.029] [PMID: 24529307]
[106]
Navarrete-Vázquez, G.; Chávez-Silva, F.; Colín-Lozano, B.; Estrada-Soto, S.; Hidalgo-Figueroa, S.; Guerrero-Álvarez, J.; Méndez, S.T.; Reyes-Vivas, H.; Oria-Hernández, J.; Canul-Canché, J.; Ortiz-Andrade, R.; Moo-Puc, R. Synthesis of nitro(benzo)thiazole acetamides and in vitro antiprotozoal effect against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis. Bioorg. Med. Chem., 2015, 23(9), 2204-2210.
[http://dx.doi.org/10.1016/j.bmc.2015.02.059] [PMID: 25801157]
[107]
Somvanshi, V.S.; Ellis, B.L.; Hu, Y.; Aroian, R.V. Nitazoxanide: nematicidal mode of action and drug combination studies. Mol. Biochem. Parasitol., 2014, 193(1), 1-8.
[http://dx.doi.org/10.1016/j.molbiopara.2013.12.002] [PMID: 24412397]
[108]
Müller, J.; Sterk, M.; Hemphill, A.; Müller, N. Characterization of Giardia lamblia WB C6 clones resistant to nitazoxanide and to metronidazole. J. Antimicrob. Chemother., 2007, 60(2), 280-287.
[http://dx.doi.org/10.1093/jac/dkm205] [PMID: 17561498]
[109]
Müller, J.; Schildknecht, P.; Müller, N. Metabolism of nitro drugs metronidazole and nitazoxanide in Giardia lamblia: characterization of a novel nitroreductase (GlNR2). J. Antimicrob. Chemother., 2013, 68(8), 1781-1789.
[http://dx.doi.org/10.1093/jac/dkt106] [PMID: 23580565]
[110]
McLuskey, K.; Gibellini, F.; Carvalho, P.; Avery, M.A.; Hunter, W.N. Inhibition of Leishmania major pteridine reductase by 2,4,6-triaminoquinazoline: structure of the NADPH ternary complex. Acta Crystallogr. D Biol. Crystallogr., 2004, 60(Pt 10), 1780-1785.
[http://dx.doi.org/10.1107/S0907444904018955] [PMID: 15388924]
[111]
Khabnadideh, S.; Pez, D.; Musso, A.; Brun, R.; Pérez, L.M.; González-Pacanowska, D.; Gilbert, I.H. Design, synthesis and evaluation of 2,4-diaminoquinazolines as inhibitors of trypanosomal and leishmanial dihydrofolate reductase. Bioorg. Med. Chem., 2005, 13(7), 2637-2649.
[http://dx.doi.org/10.1016/j.bmc.2005.01.025] [PMID: 15755663]
[112]
Croft, S.L.; Coombs, G.H. Leishmaniasis-current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol., 2003, 19(11), 502-508.
[http://dx.doi.org/10.1016/j.pt.2003.09.008] [PMID: 14580961]
[113]
Estevez, Y.; Quiliano, M.; Burguete, A.; Cabanillas, B.; Zimic, M.; Málaga, E.; Verástegui, M.; Pérez-Silanes, S.; Aldana, I.; Monge, A.; Castillo, D.; Deharo, E. Trypanocidal properties, structure-activity relationship and computational studies of quinoxaline 1,4-di-N-oxide derivatives. Exp. Parasitol., 2011, 127(4), 745-751.
[http://dx.doi.org/10.1016/j.exppara.2011.01.009] [PMID: 21272583]
[114]
Benitez, D.; Cabrera, M.; Hernández, P.; Boiani, L.; Lavaggi, M.L.; Di Maio, R.; Yaluff, G.; Serna, E.; Torres, S.; Ferreira, M.E.; Vera de Bilbao, N.; Torres, E.; Pérez-Silanes, S.; Solano, B.; Moreno, E.; Aldana, I.; López de Ceráin, A.; Cerecetto, H.; González, M.; Monge, A. 3-Trifluoromethylquinoxaline N,N′-dioxides as anti-trypanosomatid agents. Identification of optimal anti-T. cruzi agents and mechanism of action studies. J. Med. Chem., 2011, 54(10), 3624-3636.
[http://dx.doi.org/10.1021/jm2002469] [PMID: 21506600]
[115]
Varela, J.; Lessa, J.A.; Lavaggi, M.L.; Beraldo, H.; Cerecetto, H.; Gonzalez, M. Coordination of 3-aminoquino-xaline-2-carbonitrile 1,4-dioxides to antimony (III) as a strategy for anti-Trypanosoma cruzi activity improvement. Med. Chem. Res., 2012, 21(12), 4120-4128.
[http://dx.doi.org/10.1007/s00044-011-9955-z]
[116]
Barea, C.; Pabón, A.; Castillo, D.; Zimic, M.; Quiliano, M.; Galiano, S.; Pérez-Silanes, S.; Monge, A.; Deharo, E.; Aldana, I. New salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-N-oxide with antileishmanial and antimalarial activities. Bioorg. Med. Chem. Lett., 2011, 21(15), 4498-4502.
[http://dx.doi.org/10.1016/j.bmcl.2011.05.125] [PMID: 21724395]
[117]
Barea, C.; Pabón, A.; Pérez-Silanes, S.; Galiano, S.; Gonzalez, G.; Monge, A.; Deharo, E.; Aldana, I. New amide derivatives of quinoxaline 1,4-di-N-oxide with leishmanicidal and antiplasmodial activities. Molecules, 2013, 18(4), 4718-4727.
[http://dx.doi.org/10.3390/molecules18044718] [PMID: 23609622]
[118]
Mendoza-Martínez, C.; Correa-Basurto, J.; Nieto-Meneses, R.; Márquez-Navarro, A.; Aguilar-Suárez, R.; Montero-Cortes, M.D.; Nogueda-Torres, B.; Suárez-Contreras, E.; Galindo-Sevilla, N.; Rojas-Rojas, Á.; Rodriguez-Lezama, A.; Hernández-Luis, F. Design, synthesis and biological evaluation of quinazoline derivatives as anti-trypano-somatid and anti-plasmodial agents. Eur. J. Med. Chem., 2015, 96, 296-307.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.028] [PMID: 25899334]
[119]
Rodrigues, J.H.S.; 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]
[120]
Cogo, J.; Kaplum, V.; Sangi, D.P.; Ueda-Nakamura, T.; Corrêa, A.G.; Nakamura, C.V. Synthesis and biological evaluation of novel 2,3-disubstituted quinoxaline derivatives as antileishmanial and antitrypanosomal agents. Eur. J. Med. Chem., 2015, 90, 107-123.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.018] [PMID: 25461316]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy