Challenges in the chemotherapy of Chagas disease: Looking for possibilities related to the differences and similarities between the parasite and host
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摘要
Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries. This short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. The primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its human host.
Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries. This short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. The primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its human host.
Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries. This short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. The primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its human host.
引文
1 Chagas C.Trypanosoma minasense(Nota preliminar).Brazil Médico 1908;22:48
2 Chagas C.Nova tripanosomiaze humana.Estudos sobre a morfolojía e o ciclo evolutivo do Schizotrypanum cruzi n.gen.,n.sp.,ajente etiolojico de nova entidade morbida do homen.Mem IOswaldo Cruz 1909;1:159-218[DOI:10.1590/S0074-02761909000200008]
3 Chagas C.Nova entidade mórbida do homem.Brazil Médico1910;24:423-447
4 Delaporte F.[Chagas,the logic and the discovery].Hist Cienc Saude Manguinhos 1994;1:39-53[PMID:11625062 DOI:10.1590/S0104-59701995000100004]
5 Kropf SP,SáMR.The discovery of Trypanosoma cruzi and Chagas disease(1908-1909):tropical medicine in Brazil.Hist Cienc Saude Manguinhos 2009;16 Suppl 1:13-34[PMID:20027916DOI:10.1590/S0104-59702009000500002]
6 Chagas C.Aula inaugural da cadeira de medicina tropical-14 de setembro de 1926.In:Chagas,Carlos.Discursos e conferências.Rio de Janeiro:A Noite,1935:137-166
7 Coura JR.Síntese histórica e evolu??o dos conhecimentos sobre a doen?a de Chagas.Rio de Janeiro:Editora Fiocruz,1997:469-486
8 Dias JC.[Cecílio Roma?a,Roma?a’s sign and Chagas’disease].Rev Soc Bras Med Trop 1997;30:407-413[PMID:9380903 DOI:10.1590/S0037-86821997000500012]
9 Costa J,Peterson T.Ecological niche modeling as a tool for understanting distributions and interactions of vectors,hosts and etiologic agentes of Chagas disease.Rio de Janeiro:Editora Fiocruz,2012:59-70
10 Argolo AM,Felix M,Pacheco R,Costa J.Doen?a de Chagas e seus principais vetores no Brasil.Rio de Janeiro:Editora Fiocruz,200811 Wendel S.Transfusion transmitted Chagas disease:is it really under control?Acta Trop 2010;115:28-34[PMID:20044970 DOI:10.1016/j.actatropica.2009.12.006]
12 Diaz-Luján C,Triquell MF,Mezzano L,Fretes RE.Placental infection by Trypanosoma cruzi,the causal agente of Chagas’disease.La Rioja:Intechopen,2012:127-148
13 Benchimol-Barbosa PR.Trends on acute Chagas’disease transmitted by oral route in Brazil:steady increase in new cases and a concealed residual fluctuation.Int J Cardiol 2010;145:494-496[PMID:19762096 DOI:10.1016/j.ijcard.2009.08.030]
14 Rey L.Parasitologia.3rd ed.Rio de Janeiro:Guanabara Koogan,200115 Coura JR,Borges-Pereira J.Chronic phase of Chagas disease:why should it be treated?A comprehensive review.Mem I Oswaldo Cruz2011;106:642-645[DOI:10.1590/S0074-02762011000600001]
16 World Health Organization.Death and DALY estimates for2004 by cause for WHO Member States:Persons,all ages(XLS)2002.[accessed 2016 Aug 2].Available from:URL:http://www.who.int/entity/healthinfo/global_burden_disease/gbddeathdaly countryestimates2004.xls
17 World Health Organization.Metrics:Disability-Adjusted Life year(DALY).2015.[accessed 2016 Aug 2].Available from:URL:http://www.who.int/healthinfo/global_burden_disease/metrics_daly/en/
18 World Health Organization.The global burden of disease:2004update(PDF).2008.[accessed 2016 Aug 2].Available from:URL:http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf
19 Reithinger R,Tarleton RL,Urbina JA,Kitron U,Gürtler RE.Eliminating Chagas disease:challenges and a roadmap.BMJ 2009;338:b1283[PMID:19366739 DOI:10.1136/bmj.b1283]
20 Conteh L,Engels T,Molyneux DH.Socioeconomic aspects of neglected tropical diseases.Lancet 2010;375:239-247[PMID:20109925 DOI:10.1016/S0140-6736(09)61422-7]
21 Hotez P,Ottesen E,Fenwick A,Molyuneux D.The neglected tropical diseases:the ancient afflictions of stigma and poverty and the prospects for theis control and elimination.In:Hot Topics in Infection and Immunity in Children.New York:Springer,2006[DOI:10.1007/0-387-33026-7_3]
22 Bonney KM.Chagas disease in the 21st century:a public health success or an emerging threat?Parasite 2014;21:11[PMID:24626257 DOI:10.1051/parasite/2014012]
23 Lafferty KD.The ecology of climate change and infectious diseases.Ecology 2009;90:888-900[PMID:19449681 DOI:10.1890/08-0079.1]
24 Reisenman CE,Lawrence G,Guerenstein PG,Gregory T,Dotson E,Hildebrand JG.Infection of kissing bugs with Trypanosoma cruzi,Tucson,Arizona,USA.Emerg Infect Dis 2010;16:400-405[PMID:20202413 DOI:10.3201/eid1603.090648]
25 Pepin J,Milord F,Mpia B,Meurice F,Ethier L,De Groof D,Bruneel H.An open clinical trial of nifurtimox for arseno-resistant Trypanosoma brucei gambiense sleeping sickness in central Zaire.Trans R Soc Trop Med Hyg 1989;83:514-517[PMID:2694491DOI:10.1016/0035-9203(89)90270-8]
26 Bock M,G?nnert R,Haberkorn A.Studies with Bay 2502 on animals.Bol Chil Parasitol 1969;24:13-19[PMID:4983545]
27 World Health Organization.WHO Model List of Essential Medicine.2015.[accessed 2016 Aug 2].Available from:URL:http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1
28 Rodriques Coura J,de Castro SL.A critical review on Chagas disease chemotherapy.Mem Inst Oswaldo Cruz 2002;97:3-24[PMID:11992141 DOI:10.1590/S0074-02762002000100001]
29 Boiani M,Piacenza L,Hernández P,Boiani L,Cerecetto H,González M,Denicola A.Mode of action of nifurtimox and N-oxide-containing heterocycles against Trypanosoma cruzi:is oxidative stress involved?Biochem Pharmacol 2010;79:1736-1745[PMID:20178775 DOI:10.1016/j.bcp.2010.02.009]
30 Haber F,Weiss J.über die Katalyse des Hydroperoxydes.Naturwis-senschaften 1932;20:948-950[DOI:10.1007/BF01504715]
31 Patterson S,Wyllie S.Nitro drugs for the treatment of trypanosomatid diseases:past,present,and future prospects.Trends Parasitol 2014;30:289-298[PMID:24776300 DOI:10.1016/j.pt.2014.04.003]
32 Barreiro EJ,Fraga CAM.Química medicinal:as bases moleculares da a??o dos f?rmacos.2ed.Porto Alegre:Artmed,2008
33 Ohnishi T,Ohashi Y,Nozu K,Inoki S.Mutagenicity of nifurtimox in Escherichia coli.Mutat Res 1980;77:241-244[DOI:10.1016/0165-1218(80)90056-7]
34 Nagel R.Genotoxicity studies with two antichagasic drugs.Mutat Res 1997;191:17-20[DOI:10.1016/0165-7992(87)90164-3]
35 Docampo R.Sensitivity of parasites to free radical damage by antiparasitic drugs.Chem Biol Interact 1990;73:1-27[PMID:2406032 DOI:10.1016/0009-2797(90)90106-W]
36 Maya JD,Bollo S,Nu?ez-Vergara LJ,Squella JA,Repetto Y,Morello A,PériéJ,Chauvière G.Trypanosoma cruzi:effect and mode of action of nitroimidazole and nitrofuran derivatives.Biochem Pharmacol 2003;65:999-1006[PMID:12623132 DOI:10.1016/S0006-2952(02)01663-5]
37 Mitscher LA,Lemke TL,Gentry EJ.Foye’s Principles of Medicinal Chemistry.6ed.Lippincott:Williams&Wilkins,2012
38 Trochine A,Creek DJ,Faral-Tello P,Barrett MP,Robello C.Benznidazole biotransformation and multiple targets in Trypanosoma cruzi revealed by metabolomics.PLoS Negl Trop Dis 2014;8:e2844[PMID:24853684 DOI:10.1371/journal.pntd.0002844]
39 Murta AC,Persechini PM,Padron Tde S,de Souza W,Guimar?es JA,Scharfstein J.Structural and functional identification of GP57/51 antigen of Trypanosoma cruzi as a cysteine proteinase.Mol Biochem Parasitol 1990;43:27-38[PMID:1705310 DOI:10.1016/0166-6851(90)90127-8]
40 Mendon?a-Previato L,Gorin PA,Braga AF,Scharfstein J,Previato JO.Chemical structure and antigenic aspects of complexes obtained from epimastigotes of Trypanosoma cruzi.Biochemistry 1983;22:4980-4987[PMID:6196053 DOI:10.1021/bi00290a016]
41 Souto-Padrón T,Campetella OE,Cazzulo JJ,de Souza W.Cysteine proteinase in Trypanosoma cruzi:immunocytochemical localization and involvement in parasite-host cell interaction.JCell Sci 1990;96(Pt 3):485-490[PMID:2229199]
42 Alvarez VE,Niemirowicz GT,Cazzulo JJ.The peptidases of Trypanosoma cruzi:digestive enzymes,virulence factors,and mediators of autophagy and programmed cell death.Biochim Bio-phys Acta 2012;1824:195-206[PMID:21621652 DOI:10.1016/j.bbapap.2011.05.011]
43 Steert K,Berg M,Mottram JC,Westrop GD,Coombs GH,Cos P,Maes L,Joossens J,Van der Veken P,Haemers A,Augustyns K.α-ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease CPB.Chem Med Chem 2010;5:1734-1748[PMID:20799311 DOI:10.1002/cmdc.201000265]
44 Ferreira RS,Simeonov A,Jadhav A,Eidam O,Mott BT,Keiser MJ,Mc Kerrow JH,Maloney DJ,Irwin JJ,Shoichet BK.Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors.J Med Chem 2010;53:4891-4905[PMID:20540517 DOI:10.1021/jm100488w]
45 Brinen LS,Hansell E,Cheng J,Roush WR,Mc Kerrow JH,Fletterick RJ.A target within the target:probing cruzain’s P1’site to define structural determinants for the Chagas’disease protease.Structure 2000;8:831-840[PMID:10997902 DOI:10.1016/S0969-2126(00)00173-8]
46 Heby O,Persson L,Rentala M.Targeting the polyamine biosynthetic enzymes:a promising approach to therapy of African sleeping sickness,Chagas’disease,and leishmaniasis.Amino Acids 2007;33:359-366[PMID:17610127 DOI:10.1007/s00726-007-0537-9]
47 Benson TJ,Mc Kie JH,Garforth J,Borges A,Fairlamb AH,Douglas KT.Rationally designed selective inhibitors of trypanothione reductase.Phenothiazines and related tricyclics as lead structures.Biochem J 1992;286(Pt 1):9-11[PMID:1355650 DOI:10.1042/bj2860009]
48 Zhang Y,Bond CS,Bailey S,Cunningham ML,Fairlamb AH,Hunter WN.The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2.3 A resolution.Protein Sci 1996;5:52-61[PMID:8771196 DOI:10.1002/pro.5560050107]
49 Aboagye-Kwarteng T,Smith K,Fairlamb AH.Molecular characterization of the trypanothione reductase gene from Crithidia fasciculata and Trypanosoma brucei:comparison with other flavoprotein disulphide oxidoreductases with respect to substrate specificity and catalytic mechanism.Mol Microbiol 1992;6:3089-3099[PMID:1453951 DOI:10.1111/j.1365-2958.1992.tb01766.x]
50 Jacoby EM,Schlichting I,Lantwin CB,Kabsch W,Krauth-Siegel RL.Crystal structure of the Trypanosoma cruzi trypanothione reductase.mepacrine complex.Proteins 1996;24:73-80[PMID:8628734 DOI:10.1002/(SICI)1097-0134(199601)24:1<73::AID-PROT5>3.0.CO;2-P]
51 Bonse S,Santelli-Rouvier C,Barbe J,Krauth-Siegel RL.Inhibition of Trypanosoma cruzi trypanothione reductase by acridines:kinetic studies and structure-activity relationships.J Med Chem 1999;42:5448-5454[PMID:10639286 DOI:10.1021/jm990386s]
52 Horvath D.A virtual screening approach applied to the search for trypanothione reductase inhibitors.J Med Chem 1997;40:2412-2423[PMID:9240356 DOI:10.1021/jm9603781]
53 Lo Presti MS,Bazán PC,Strauss M,Báez AL,Rivarola HW,Paglini-Oliva PA.Trypanothione reductase inhibitors:Overview of the action of thioridazine in different stages of Chagas disease.Acta Trop 2015;145:79-87[PMID:25733492 DOI:10.1016/j.acta tropica.2015.02.012]
54 Sola I,CastellàS,Viayna E,Galdeano C,Taylor MC,Gbedema SY,Pérez B,Clos MV,Jones DC,Fairlamb AH,Wright CW,Kelly JM,Mu?oz-Torrero D.Synthesis,biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal-antiplasmodial activity.Bioorg Med Chem 2015;23:5156-5167[PMID:25678015 DOI:10.1016/j.bmc.2015.01.031]
55 Mc Kie JH,Garforth J,Jaouhari R,Chan C,Yin H,Besheya T,Fairlamb AH,Douglas KT.Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate:potential rational drug design lead frameworks.Amino Acids 2001;20:145-153[PMID:11332449 DOI:10.1007/s007260170055]
56 Nardy AF,Freire-de-Lima CG,Pérez AR,Morrot A.Role of Trypanosoma cruzi Trans-sialidase on the Escape from Host Immune Surveillance.Front Microbiol 2016;7:348[PMID:27047464 DOI:10.3389/fmicb.2016.00348]
57 Colli W.Trans-sialidase:a unique enzyme activity discovered in the protozoan Trypanosoma cruzi.FASEB J 1993;7:1257-1264[PMID:8405811]
58 Miller BR,Roitberg AE.Trypanosoma cruzi trans-sialidase as a drug target against Chagas disease(American trypanosomiasis).Future Med Chem 2013;5:1889-1900[PMID:24144418 DOI:10.4155/fmc.13.129]
59 Agusti R,Couto AS,Campetella OE,Frasch AC,de Lederkremer RM.The trans-sialidase of Trypanosoma cruzi is anchored by two different lipids.Glycobiology 1997;7:731-735[PMID:9376675DOI:10.1093/glycob/7.6.731]
60 Giorgi ME,de Lederkremer RM.Trans-sialidase and mucins of Trypanosoma cruzi:an important interplay for the parasite.Carbohydr Res 2011;346:1389-1393[PMID:21645882 DOI:10.1016/j.carres.2011.04.006]
61 Pereira-Chioccola VL,Acosta-Serrano A,Correia de Almeida I,Ferguson MA,Souto-Padron T,Rodrigues MM,Travassos LR,Schenkman S.Mucin-like molecules form a negatively charged coat that protects Trypanosoma cruzi trypomastigotes from killing by human anti-alpha-galactosyl antibodies.J Cell Sci 2000;113(Pt
7):1299-1307[PMID:10704380]
62 Damager I,Buchini S,Amaya MF,Buschiazzo A,Alzari P,Frasch AC,Watts A,Withers SG.Kinetic and mechanistic analysis of Trypanosoma cruzi trans-sialidase reveals a classical ping-pong mechanism with acid/base catalysis.Biochemistry 2008;47:3507-3512[PMID:18284211 DOI:10.1021/bi7024832]
63 Paris G,Ratier L,Amaya MF,Nguyen T,Alzari PM,Frasch AC.Asialidase mutant displaying trans-sialidase activity.J Mol Biol 2005;345:923-934[PMID:15588836 DOI:10.1016/j.jmb.2004.09.031]
64 Watts AG,Damager I,Amaya ML,Buschiazzo A,Alzari P,Frasch AC,Withers SG.Trypanosoma cruzi trans-sialidase operates through a covalent sialyl-enzyme intermediate:tyrosine is the catalytic nucleophile.J Am Chem Soc 2003;125:7532-7533[PMID:12812490 DOI:10.1021/ja0344967]
65 AgustíR,París G,Ratier L,Frasch AC,de Lederkremer RM.Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo.Glycobiology 2004;14:659-670[PMID:15070857 DOI:10.1093/glycob/cwh079]
66 Streicher H,Busse H.Building a successful structural motif into sialylmimetics-cyclohexenephosphonate monoesters as pseudosialosides with promising inhibitory properties.Bioorg Med Chem2006;14:1047-1057[PMID:16230015 DOI:10.1016/j.bmc.2005.09.025]
67 Neres J,Bonnet P,Edwards PN,Kotian PL,Buschiazzo A,Alzari PM,Bryce RA,Douglas KT.Benzoic acid and pyridine derivatives as inhibitors of Trypanosoma cruzi trans-sialidase.Bioorg Med Chem 2007;15:2106-2119[PMID:17218104 DOI:10.1016/j.bmc.2006.12.024]
68 Kim JH,Ryu HW,Shim JH,Park KH,Withers SG.Development of new and selective Trypanosoma cruzi trans-sialidase inhibitors from sulfonamide chalcones and their derivatives.Chembiochem 2009;10:2475-2479[PMID:19780074 DOI:10.1002/cbic.200900108]
69 Arioka S,Sakagami M,Uematsu R,Yamaguchi H,Togame H,Takemoto H,Hinou H,Nishimura S.Potent inhibitor scaffold against Trypanosoma cruzi trans-sialidase.Bioorg Med Chem 2010;18:1633-1640[PMID:20097567 DOI:10.1016/j.bmc.2009.12.062]
70 Brown GD.The biosynthesis of steroids and triterpenoids.Nal Prod Rep 1998;15:653-696[DOI:10.1039/a815653y]
71 Mc Cabe RE,Araujo FG,Remington JS.Ketoconazole protects against infection with Trypanosoma cruzi in a murine model.Am JTrop Med Hyg 1983;32:960-962[PMID:6312824]
72 Sueth-Santiago V,Franklim TN,Lopes ND,Lima MEF.CYP51:uma boa ideia?Rev Vir Quím 2015;7:539-575[DOI:10.5935/1984-6835.20150024]
73 Urbina JA.Lipid biosynthesis pathways as chemotherapeutic targets in kinetoplastid parasites.Parasitology 1997;114 Suppl:S91-S99[PMID:9309771]
74 Lepesheva GI,Virus C,Waterman MR.Conservation in the CYP51 family.Role of the B’helix/BC loop and helices F and Gin enzymatic function.Biochemistry 2003;42:9091-9101[PMID:12885242 DOI:10.1021/bi034663f]
75 Lepesheva GI,Zaitseva NG,Nes WD,Zhou W,Arase M,Liu J,Hill GC,Waterman MR.CYP51 from Trypanosoma cruzi:a phylaspecific residue in the B’helix defines substrate preferences of sterol 14alpha-demethylase.J Biol Chem 2006;281:3577-3585[PMID:16321980 DOI:10.1074/jbc.M510317200]
76 Dias LC,Dessoy MA,Silva JJN,Thiemann OH,Oliva G,Andricopulo AD.Quimioterapia da doen?a de Chagas:estado da arte e perspectivas no desenvolvimento de novos fármacos.Quím Nova2009;32:2444-2457[DOI:10.1590/S0100-40422009000900038]
77 Villalta F,Dobish MC,Nde PN,Kleshchenko YY,Hargrove TY,Johnson CA,Waterman MR,Johnston JN,Lepesheva GI.VNIcures acute and chronic experimental Chagas disease.J Infect Dis2013;208:504-511[PMID:23372180 DOI:10.1093/infdis/jit042]
78 Mc Cabe RE,Remington JS,Araujo FG.Ketoconazole promotes parasitological cure of mice infected with Trypanosoma cruzi.Trans R Soc Trop Med Hyg 1987;81:613-615[PMID:3127963DOI:10.1016/0035-9203(87)90430-5]
79 Pfaller MA,Krogstad DJ.Imidazole and polyene activity against chloroquine-resistant Plasmodium falciparum.J Infect Dis 1981;144:372-375[PMID:6270216 DOI:10.1093/infdis/144.4.372]
80 Berman JD.Activity of imidazoles against Leishmania tropica in human macrophage cultures.Am J Trop Med Hyg 1981;30:566-569[PMID:6266261]
81 Urbina JA.Ergosterol biosynthesis and drug development for Chagas disease.Mem Inst Oswaldo Cruz 2009;104 Suppl 1:311-318[PMID:19753490 DOI:10.1590/S0074-02762009000900041]
82 Shapiro RS,Robbins N,Cowen LE.Regulatory circuitry governing fungal development,drug resistance,and disease.Microbiol Mol Biol Rev 2011;75:213-267[PMID:21646428]
83 Abe F,Usui K,Hiraki T.Fluconazole modulates membrane rigidity,heterogeneity,and water penetration into the plasma membrane in Saccharomyces cerevisiae.Biochemistry 2009;48:8494-8504[PMID:19670905]
84 Franklim TN,Freire-de-Lima L,de Nazareth SáDiniz J,Previato JO,Castro RN,Mendon?a-Previato L,de Lima ME.Design,synthesis and trypanocidal evaluation of novel 1,2,4-triazoles-
3-thiones derived from natural piperine.Molecules 2013;18:6366-6382[PMID:23760033 DOI:10.3390/molecules18066366]
85 Warrilow AG,Parker JE,Kelly DE,Kelly SL.Azole affinity of sterol 14α-demethylase(CYP51)enzymes from Candida albicans and Homo sapiens.Antimicrob Agents Chemother 2013;57:1352-1360[PMID:23274672 DOI:10.1128/AAC.02067-12]
86 Conley A,Mapes S,Corbin CJ,Greger D,Walters K,Trant J,Graham S.A comparative approach to structure-function studies of mammalian aromatases.J Steroid Biochem Mol Biol 2001;79:289-297[PMID:11850235 DOI:10.1016/S0960-0760(01)00145-5]
87 Zarn JA,Brüschweiler BJ,Schlatter JR.Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14 alphademethylase and aromatase.Environ Health Perspect 2003;111:255-261[PMID:12611652 DOI:10.1289/ehp.5785]
88 Heald R,Nogales E.Microtubule dynamics.J Cell Sci 2002;115:3-4[PMID:11801717]
89 Westermann S,Weber K.Post-translational modifications regulate microtubule function.Nat Rev Mol Cell Biol 2003;4:938-947[PMID:14685172 DOI:10.1038/nrm1260]
90 Perez EA.Microtubule inhibitors:Differentiating tubulin-inhibiting agents based on mechanisms of action,clinical activity,and resistance.Mol Cancer Ther 2009;8:2086-2095[PMID:19671735 DOI:10.1158/1535-7163.MCT-09-0366]
91 Zhou J,Giannakakou P.Targeting microtubules for cancer chemotherapy.Curr Med Chem Anticancer Agents 2005;5:65-71[PMID:15720262 DOI:10.2174/1568011053352569]
92 Nogales E.Structural insight into microtubule function.Annu Rev Biophys Biomol Struct 2001;30:397-420[PMID:11441808 DOI:10.1146/annurev.biophys.30.1.397]
93 Akhmanova A,Steinmetz MO.Tracking the ends:a dynamic protein network controls the fate of microtubule tips.Nat Rev Mol Cell Biol 2008;9:309-322[PMID:18322465 DOI:10.1038/nrm2369]
94 Kuppens IE.Current state of the art of new tubulin inhibitors in the clinic.Curr Clin Pharmacol 2006;1:57-70[PMID:18666378DOI:10.2174/157488406775268200]
95 Werbovetz KA.Tubulin as an antiprotozoal drug target.Mini Rev Med Chem 2002;2:519-529[PMID:12370037 DOI:10.2174/1389557023405648]
96 Kilmartin JV.Purification of yeast tubulin by self-assembly in vitro.Biochemistry 1981;20:3629-3633[PMID:7020758 DOI:10.1021/bi00515a050]
97 Dawson PJ,Gutteridge WE,Gull K.A comparison of the interaction of anthelmintic benzimidazoles with tubulin isolated from mammalian tissue and the parasitic nematode Ascaridia galli.Biochem Pharmacol 1984;33:1069-1074[PMID:6712717 DOI:10.1016/0006-2952(84)90515-X]
98 Werbovetz KA,Sackett DL,Delfín D,Bhattacharya G,Salem M,Obrzut T,Rattendi D,Bacchi C.Selective antimicrotubule activity of N1-phenyl-3,5-dinitro-N4,N4-di-n-propylsulfanilamide(GB-II-5)against kinetoplastid parasites.Mol Pharmacol 2003;64:1325-1333[PMID:14645662 DOI:10.1124/mol.64.6.1325]
99 Zhong B,Cai X,Chennamaneni S,Yi X,Liu L,Pink JJ,Dowlati A,Xu Y,Zhou A,Su B.From COX-2 inhibitor nimesulide to potent anti-cancer agent:synthesis,in vitro,in vivo and pharmacokinetic evaluation.Eur J Med Chem 2012;47:432-444[PMID:22119125DOI:10.1016/j.ejmech.2011.11.012]
100 Lu Y,Chen J,Xiao M,Li W,Miller DD.An overview of tubulin inhibitors that interact with the colchicine binding site.Pharm Res2012;29:2943-2971[PMID:22814904 DOI:10.1007/s11095-012-0828-z]
101 Ravelli RB,Gigant B,Curmi PA,Jourdain I,Lachkar S,Sobel A,Knossow M.Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain.Nature 2004;428:198-202[PMID:15014504 DOI:10.1038/nature02393]
102 Cormier A,Knossow M,Wang C,Gigant B.The binding of vinca domain agents to tubulin:structural and biochemical studies.Methods Cell Biol 2010;95:373-390[PMID:20466145 DOI:10.1016/S0091-679X(10)95020-6]
103 Noble RL.The discovery of the vinca alkaloids--chemotherapeutic agents against cancer.Biochem Cell Biol 1990;68:1344-1351[PMID:2085431 DOI:10.1139/o90-197]
104 Sottomayor M,López-Serrano M,Di Cosmo F,Ros BarcelóA.Purification and characterization of alpha-3’,4’-anhydrovinblastine synthase(peroxidase-like)from Catharanthus roseus(L.)G.Don.FEBS Lett 1998;428:299-303[PMID:9654153 DOI:10.1016/S0014-5793(98)00551-1]
105 Almagro L,Fernández-Pérez F,Pedre?o MA.Indole alkaloids from Catharanthus roseus:bioproduction and their effect on human health.Molecules 2015;20:2973-3000[PMID:25685907 DOI:10.3390/molecules20022973]
106 Brand?o HN,David JP,Couto RD,Nascimento JAP,David JM.Química e farmacologia dos quimioterápicos antineoplásicos derivados de plantas.Quím Nova 2010;33:1359-1369[DOI:10.1590/S0100-40422010000600026]
107 Panda D,Jordan MA,Chu KC,Wilson L.Differential effects of vinblastine on polymerization and dynamics at opposite microtubule ends.J Biol Chem 1996;271:29807-29812[PMID:8939919 DOI:10.1074/jbc.271.47.29807]
108 Yang H,Ganguly A,Cabral F.Inhibition of cell migration and cell division correlates with distinct effects of microtubule inhibiting drugs.J Biol Chem 2010;285:32242-32250[PMID:20696757DOI:10.1074/jbc.M110.160820]
109 Amos LA,L?we J.How Taxol stabilises microtubule structure.Chem Biol 1999;6:R65-R69[PMID:10074470 DOI:10.1016/S1074-5521(99)89002-4]
110 Ojima I,Habus I,Zhao M,Zucco M,Park YH,Sun CM,Brigaud T.New and eficient approaches to the semisynthesis of taxol and its C-13 side chain analogs by means ofβ-lactam synthon method.Tetrahedron 1992;48:6985-7012[DOI:10.1016/S0040-4020(01)91210-4]
111 Fu Y,Li S,Zu Y,Yang G,Yang Z,Luo M,Jiang S,Wink M,Efferth T.Medicinal chemistry of paclitaxel and its analogues.Curr Med Chem 2009;16:3966-3985[PMID:19747129 DOI:10.2174/092986709789352277]
112 Baum SG,Wittner M,Nadler JP,Horwitz SB,Dennis JE,Schiff PB,Tanowitz HB.Taxol,a microtubule stabilizing agent,blocks the replication of Trypanosoma cruzi.Proc Natl Acad Sci USA 1981;78:4571-4575[PMID:6117077 DOI:10.1073/pnas.78.7.4571]
113 Freire-de-Lima L,Ribeiro TS,Rocha GM,Brand?o BA,Romeiro A,Mendon?a-Previato L,Previato JO,de Lima ME,de Carvalho TM,Heise N.The toxic effects of piperine against Trypanosoma cruzi:ultrastructural alterations and reversible blockage of cytokinesis in epimastigote forms.Parasitol Res 2008;102:1059-1067[PMID:18224488 DOI:10.1007/s00436-008-0876-9]
114 Gupta KK,Bharne SS,Rathinasamy K,Naik NR,Panda D.Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding.FEBS J 2006;273:5320-5332[PMID:17069615 DOI:10.1111/j.1742-4658.2006.05525.x]
115 Banerjee M,Singh P,Panda D.Curcumin suppresses the dynamic instability of microtubules,activates the mitotic checkpoint and induces apoptosis in MCF-7 cells.FEBS J 2010;277:3437-3448[PMID:20646066]
116 Chakraborti S,Das L,Kapoor N,Das A,Dwivedi V,Poddar A,Chakraborti G,Janik M,Basu G,Panda D,Chakrabarti P,Surolia A,Bhattacharyya B.Curcumin recognizes a unique binding site of tubulin.J Med Chem 2011;54:6183-6196[PMID:21830815 DOI:10.1021/jm2004046]
117 Sueth-Santiago V,Moraes JB,Sobral Alves ES,Vannier-Santos MA,Freire-de-Lima CG,Castro RN,Mendes-Silva GP,Del Cistia CN,Magalh?es LG,Andricopulo AD,Sant Anna CM,Decoté-Ricardo D,Freire de Lima ME.The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi:Cytotoxicity,Ultrastructural Alterations and Molecular Modeling Studies.PLoSOne 2016;11:e0162926[PMID:27658305 DOI:10.1371/journal.pone.0162926]
2 Chagas C.Nova tripanosomiaze humana.Estudos sobre a morfolojía e o ciclo evolutivo do Schizotrypanum cruzi n.gen.,n.sp.,ajente etiolojico de nova entidade morbida do homen.Mem IOswaldo Cruz 1909;1:159-218[DOI:10.1590/S0074-02761909000200008]
3 Chagas C.Nova entidade mórbida do homem.Brazil Médico1910;24:423-447
4 Delaporte F.[Chagas,the logic and the discovery].Hist Cienc Saude Manguinhos 1994;1:39-53[PMID:11625062 DOI:10.1590/S0104-59701995000100004]
5 Kropf SP,SáMR.The discovery of Trypanosoma cruzi and Chagas disease(1908-1909):tropical medicine in Brazil.Hist Cienc Saude Manguinhos 2009;16 Suppl 1:13-34[PMID:20027916DOI:10.1590/S0104-59702009000500002]
6 Chagas C.Aula inaugural da cadeira de medicina tropical-14 de setembro de 1926.In:Chagas,Carlos.Discursos e conferências.Rio de Janeiro:A Noite,1935:137-166
7 Coura JR.Síntese histórica e evolu??o dos conhecimentos sobre a doen?a de Chagas.Rio de Janeiro:Editora Fiocruz,1997:469-486
8 Dias JC.[Cecílio Roma?a,Roma?a’s sign and Chagas’disease].Rev Soc Bras Med Trop 1997;30:407-413[PMID:9380903 DOI:10.1590/S0037-86821997000500012]
9 Costa J,Peterson T.Ecological niche modeling as a tool for understanting distributions and interactions of vectors,hosts and etiologic agentes of Chagas disease.Rio de Janeiro:Editora Fiocruz,2012:59-70
10 Argolo AM,Felix M,Pacheco R,Costa J.Doen?a de Chagas e seus principais vetores no Brasil.Rio de Janeiro:Editora Fiocruz,200811 Wendel S.Transfusion transmitted Chagas disease:is it really under control?Acta Trop 2010;115:28-34[PMID:20044970 DOI:10.1016/j.actatropica.2009.12.006]
12 Diaz-Luján C,Triquell MF,Mezzano L,Fretes RE.Placental infection by Trypanosoma cruzi,the causal agente of Chagas’disease.La Rioja:Intechopen,2012:127-148
13 Benchimol-Barbosa PR.Trends on acute Chagas’disease transmitted by oral route in Brazil:steady increase in new cases and a concealed residual fluctuation.Int J Cardiol 2010;145:494-496[PMID:19762096 DOI:10.1016/j.ijcard.2009.08.030]
14 Rey L.Parasitologia.3rd ed.Rio de Janeiro:Guanabara Koogan,200115 Coura JR,Borges-Pereira J.Chronic phase of Chagas disease:why should it be treated?A comprehensive review.Mem I Oswaldo Cruz2011;106:642-645[DOI:10.1590/S0074-02762011000600001]
16 World Health Organization.Death and DALY estimates for2004 by cause for WHO Member States:Persons,all ages(XLS)2002.[accessed 2016 Aug 2].Available from:URL:http://www.who.int/entity/healthinfo/global_burden_disease/gbddeathdaly countryestimates2004.xls
17 World Health Organization.Metrics:Disability-Adjusted Life year(DALY).2015.[accessed 2016 Aug 2].Available from:URL:http://www.who.int/healthinfo/global_burden_disease/metrics_daly/en/
18 World Health Organization.The global burden of disease:2004update(PDF).2008.[accessed 2016 Aug 2].Available from:URL:http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf
19 Reithinger R,Tarleton RL,Urbina JA,Kitron U,Gürtler RE.Eliminating Chagas disease:challenges and a roadmap.BMJ 2009;338:b1283[PMID:19366739 DOI:10.1136/bmj.b1283]
20 Conteh L,Engels T,Molyneux DH.Socioeconomic aspects of neglected tropical diseases.Lancet 2010;375:239-247[PMID:20109925 DOI:10.1016/S0140-6736(09)61422-7]
21 Hotez P,Ottesen E,Fenwick A,Molyuneux D.The neglected tropical diseases:the ancient afflictions of stigma and poverty and the prospects for theis control and elimination.In:Hot Topics in Infection and Immunity in Children.New York:Springer,2006[DOI:10.1007/0-387-33026-7_3]
22 Bonney KM.Chagas disease in the 21st century:a public health success or an emerging threat?Parasite 2014;21:11[PMID:24626257 DOI:10.1051/parasite/2014012]
23 Lafferty KD.The ecology of climate change and infectious diseases.Ecology 2009;90:888-900[PMID:19449681 DOI:10.1890/08-0079.1]
24 Reisenman CE,Lawrence G,Guerenstein PG,Gregory T,Dotson E,Hildebrand JG.Infection of kissing bugs with Trypanosoma cruzi,Tucson,Arizona,USA.Emerg Infect Dis 2010;16:400-405[PMID:20202413 DOI:10.3201/eid1603.090648]
25 Pepin J,Milord F,Mpia B,Meurice F,Ethier L,De Groof D,Bruneel H.An open clinical trial of nifurtimox for arseno-resistant Trypanosoma brucei gambiense sleeping sickness in central Zaire.Trans R Soc Trop Med Hyg 1989;83:514-517[PMID:2694491DOI:10.1016/0035-9203(89)90270-8]
26 Bock M,G?nnert R,Haberkorn A.Studies with Bay 2502 on animals.Bol Chil Parasitol 1969;24:13-19[PMID:4983545]
27 World Health Organization.WHO Model List of Essential Medicine.2015.[accessed 2016 Aug 2].Available from:URL:http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1
28 Rodriques Coura J,de Castro SL.A critical review on Chagas disease chemotherapy.Mem Inst Oswaldo Cruz 2002;97:3-24[PMID:11992141 DOI:10.1590/S0074-02762002000100001]
29 Boiani M,Piacenza L,Hernández P,Boiani L,Cerecetto H,González M,Denicola A.Mode of action of nifurtimox and N-oxide-containing heterocycles against Trypanosoma cruzi:is oxidative stress involved?Biochem Pharmacol 2010;79:1736-1745[PMID:20178775 DOI:10.1016/j.bcp.2010.02.009]
30 Haber F,Weiss J.über die Katalyse des Hydroperoxydes.Naturwis-senschaften 1932;20:948-950[DOI:10.1007/BF01504715]
31 Patterson S,Wyllie S.Nitro drugs for the treatment of trypanosomatid diseases:past,present,and future prospects.Trends Parasitol 2014;30:289-298[PMID:24776300 DOI:10.1016/j.pt.2014.04.003]
32 Barreiro EJ,Fraga CAM.Química medicinal:as bases moleculares da a??o dos f?rmacos.2ed.Porto Alegre:Artmed,2008
33 Ohnishi T,Ohashi Y,Nozu K,Inoki S.Mutagenicity of nifurtimox in Escherichia coli.Mutat Res 1980;77:241-244[DOI:10.1016/0165-1218(80)90056-7]
34 Nagel R.Genotoxicity studies with two antichagasic drugs.Mutat Res 1997;191:17-20[DOI:10.1016/0165-7992(87)90164-3]
35 Docampo R.Sensitivity of parasites to free radical damage by antiparasitic drugs.Chem Biol Interact 1990;73:1-27[PMID:2406032 DOI:10.1016/0009-2797(90)90106-W]
36 Maya JD,Bollo S,Nu?ez-Vergara LJ,Squella JA,Repetto Y,Morello A,PériéJ,Chauvière G.Trypanosoma cruzi:effect and mode of action of nitroimidazole and nitrofuran derivatives.Biochem Pharmacol 2003;65:999-1006[PMID:12623132 DOI:10.1016/S0006-2952(02)01663-5]
37 Mitscher LA,Lemke TL,Gentry EJ.Foye’s Principles of Medicinal Chemistry.6ed.Lippincott:Williams&Wilkins,2012
38 Trochine A,Creek DJ,Faral-Tello P,Barrett MP,Robello C.Benznidazole biotransformation and multiple targets in Trypanosoma cruzi revealed by metabolomics.PLoS Negl Trop Dis 2014;8:e2844[PMID:24853684 DOI:10.1371/journal.pntd.0002844]
39 Murta AC,Persechini PM,Padron Tde S,de Souza W,Guimar?es JA,Scharfstein J.Structural and functional identification of GP57/51 antigen of Trypanosoma cruzi as a cysteine proteinase.Mol Biochem Parasitol 1990;43:27-38[PMID:1705310 DOI:10.1016/0166-6851(90)90127-8]
40 Mendon?a-Previato L,Gorin PA,Braga AF,Scharfstein J,Previato JO.Chemical structure and antigenic aspects of complexes obtained from epimastigotes of Trypanosoma cruzi.Biochemistry 1983;22:4980-4987[PMID:6196053 DOI:10.1021/bi00290a016]
41 Souto-Padrón T,Campetella OE,Cazzulo JJ,de Souza W.Cysteine proteinase in Trypanosoma cruzi:immunocytochemical localization and involvement in parasite-host cell interaction.JCell Sci 1990;96(Pt 3):485-490[PMID:2229199]
42 Alvarez VE,Niemirowicz GT,Cazzulo JJ.The peptidases of Trypanosoma cruzi:digestive enzymes,virulence factors,and mediators of autophagy and programmed cell death.Biochim Bio-phys Acta 2012;1824:195-206[PMID:21621652 DOI:10.1016/j.bbapap.2011.05.011]
43 Steert K,Berg M,Mottram JC,Westrop GD,Coombs GH,Cos P,Maes L,Joossens J,Van der Veken P,Haemers A,Augustyns K.α-ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease CPB.Chem Med Chem 2010;5:1734-1748[PMID:20799311 DOI:10.1002/cmdc.201000265]
44 Ferreira RS,Simeonov A,Jadhav A,Eidam O,Mott BT,Keiser MJ,Mc Kerrow JH,Maloney DJ,Irwin JJ,Shoichet BK.Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors.J Med Chem 2010;53:4891-4905[PMID:20540517 DOI:10.1021/jm100488w]
45 Brinen LS,Hansell E,Cheng J,Roush WR,Mc Kerrow JH,Fletterick RJ.A target within the target:probing cruzain’s P1’site to define structural determinants for the Chagas’disease protease.Structure 2000;8:831-840[PMID:10997902 DOI:10.1016/S0969-2126(00)00173-8]
46 Heby O,Persson L,Rentala M.Targeting the polyamine biosynthetic enzymes:a promising approach to therapy of African sleeping sickness,Chagas’disease,and leishmaniasis.Amino Acids 2007;33:359-366[PMID:17610127 DOI:10.1007/s00726-007-0537-9]
47 Benson TJ,Mc Kie JH,Garforth J,Borges A,Fairlamb AH,Douglas KT.Rationally designed selective inhibitors of trypanothione reductase.Phenothiazines and related tricyclics as lead structures.Biochem J 1992;286(Pt 1):9-11[PMID:1355650 DOI:10.1042/bj2860009]
48 Zhang Y,Bond CS,Bailey S,Cunningham ML,Fairlamb AH,Hunter WN.The crystal structure of trypanothione reductase from the human pathogen Trypanosoma cruzi at 2.3 A resolution.Protein Sci 1996;5:52-61[PMID:8771196 DOI:10.1002/pro.5560050107]
49 Aboagye-Kwarteng T,Smith K,Fairlamb AH.Molecular characterization of the trypanothione reductase gene from Crithidia fasciculata and Trypanosoma brucei:comparison with other flavoprotein disulphide oxidoreductases with respect to substrate specificity and catalytic mechanism.Mol Microbiol 1992;6:3089-3099[PMID:1453951 DOI:10.1111/j.1365-2958.1992.tb01766.x]
50 Jacoby EM,Schlichting I,Lantwin CB,Kabsch W,Krauth-Siegel RL.Crystal structure of the Trypanosoma cruzi trypanothione reductase.mepacrine complex.Proteins 1996;24:73-80[PMID:8628734 DOI:10.1002/(SICI)1097-0134(199601)24:1<73::AID-PROT5>3.0.CO;2-P]
51 Bonse S,Santelli-Rouvier C,Barbe J,Krauth-Siegel RL.Inhibition of Trypanosoma cruzi trypanothione reductase by acridines:kinetic studies and structure-activity relationships.J Med Chem 1999;42:5448-5454[PMID:10639286 DOI:10.1021/jm990386s]
52 Horvath D.A virtual screening approach applied to the search for trypanothione reductase inhibitors.J Med Chem 1997;40:2412-2423[PMID:9240356 DOI:10.1021/jm9603781]
53 Lo Presti MS,Bazán PC,Strauss M,Báez AL,Rivarola HW,Paglini-Oliva PA.Trypanothione reductase inhibitors:Overview of the action of thioridazine in different stages of Chagas disease.Acta Trop 2015;145:79-87[PMID:25733492 DOI:10.1016/j.acta tropica.2015.02.012]
54 Sola I,CastellàS,Viayna E,Galdeano C,Taylor MC,Gbedema SY,Pérez B,Clos MV,Jones DC,Fairlamb AH,Wright CW,Kelly JM,Mu?oz-Torrero D.Synthesis,biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal-antiplasmodial activity.Bioorg Med Chem 2015;23:5156-5167[PMID:25678015 DOI:10.1016/j.bmc.2015.01.031]
55 Mc Kie JH,Garforth J,Jaouhari R,Chan C,Yin H,Besheya T,Fairlamb AH,Douglas KT.Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate:potential rational drug design lead frameworks.Amino Acids 2001;20:145-153[PMID:11332449 DOI:10.1007/s007260170055]
56 Nardy AF,Freire-de-Lima CG,Pérez AR,Morrot A.Role of Trypanosoma cruzi Trans-sialidase on the Escape from Host Immune Surveillance.Front Microbiol 2016;7:348[PMID:27047464 DOI:10.3389/fmicb.2016.00348]
57 Colli W.Trans-sialidase:a unique enzyme activity discovered in the protozoan Trypanosoma cruzi.FASEB J 1993;7:1257-1264[PMID:8405811]
58 Miller BR,Roitberg AE.Trypanosoma cruzi trans-sialidase as a drug target against Chagas disease(American trypanosomiasis).Future Med Chem 2013;5:1889-1900[PMID:24144418 DOI:10.4155/fmc.13.129]
59 Agusti R,Couto AS,Campetella OE,Frasch AC,de Lederkremer RM.The trans-sialidase of Trypanosoma cruzi is anchored by two different lipids.Glycobiology 1997;7:731-735[PMID:9376675DOI:10.1093/glycob/7.6.731]
60 Giorgi ME,de Lederkremer RM.Trans-sialidase and mucins of Trypanosoma cruzi:an important interplay for the parasite.Carbohydr Res 2011;346:1389-1393[PMID:21645882 DOI:10.1016/j.carres.2011.04.006]
61 Pereira-Chioccola VL,Acosta-Serrano A,Correia de Almeida I,Ferguson MA,Souto-Padron T,Rodrigues MM,Travassos LR,Schenkman S.Mucin-like molecules form a negatively charged coat that protects Trypanosoma cruzi trypomastigotes from killing by human anti-alpha-galactosyl antibodies.J Cell Sci 2000;113(Pt
7):1299-1307[PMID:10704380]
62 Damager I,Buchini S,Amaya MF,Buschiazzo A,Alzari P,Frasch AC,Watts A,Withers SG.Kinetic and mechanistic analysis of Trypanosoma cruzi trans-sialidase reveals a classical ping-pong mechanism with acid/base catalysis.Biochemistry 2008;47:3507-3512[PMID:18284211 DOI:10.1021/bi7024832]
63 Paris G,Ratier L,Amaya MF,Nguyen T,Alzari PM,Frasch AC.Asialidase mutant displaying trans-sialidase activity.J Mol Biol 2005;345:923-934[PMID:15588836 DOI:10.1016/j.jmb.2004.09.031]
64 Watts AG,Damager I,Amaya ML,Buschiazzo A,Alzari P,Frasch AC,Withers SG.Trypanosoma cruzi trans-sialidase operates through a covalent sialyl-enzyme intermediate:tyrosine is the catalytic nucleophile.J Am Chem Soc 2003;125:7532-7533[PMID:12812490 DOI:10.1021/ja0344967]
65 AgustíR,París G,Ratier L,Frasch AC,de Lederkremer RM.Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo.Glycobiology 2004;14:659-670[PMID:15070857 DOI:10.1093/glycob/cwh079]
66 Streicher H,Busse H.Building a successful structural motif into sialylmimetics-cyclohexenephosphonate monoesters as pseudosialosides with promising inhibitory properties.Bioorg Med Chem2006;14:1047-1057[PMID:16230015 DOI:10.1016/j.bmc.2005.09.025]
67 Neres J,Bonnet P,Edwards PN,Kotian PL,Buschiazzo A,Alzari PM,Bryce RA,Douglas KT.Benzoic acid and pyridine derivatives as inhibitors of Trypanosoma cruzi trans-sialidase.Bioorg Med Chem 2007;15:2106-2119[PMID:17218104 DOI:10.1016/j.bmc.2006.12.024]
68 Kim JH,Ryu HW,Shim JH,Park KH,Withers SG.Development of new and selective Trypanosoma cruzi trans-sialidase inhibitors from sulfonamide chalcones and their derivatives.Chembiochem 2009;10:2475-2479[PMID:19780074 DOI:10.1002/cbic.200900108]
69 Arioka S,Sakagami M,Uematsu R,Yamaguchi H,Togame H,Takemoto H,Hinou H,Nishimura S.Potent inhibitor scaffold against Trypanosoma cruzi trans-sialidase.Bioorg Med Chem 2010;18:1633-1640[PMID:20097567 DOI:10.1016/j.bmc.2009.12.062]
70 Brown GD.The biosynthesis of steroids and triterpenoids.Nal Prod Rep 1998;15:653-696[DOI:10.1039/a815653y]
71 Mc Cabe RE,Araujo FG,Remington JS.Ketoconazole protects against infection with Trypanosoma cruzi in a murine model.Am JTrop Med Hyg 1983;32:960-962[PMID:6312824]
72 Sueth-Santiago V,Franklim TN,Lopes ND,Lima MEF.CYP51:uma boa ideia?Rev Vir Quím 2015;7:539-575[DOI:10.5935/1984-6835.20150024]
73 Urbina JA.Lipid biosynthesis pathways as chemotherapeutic targets in kinetoplastid parasites.Parasitology 1997;114 Suppl:S91-S99[PMID:9309771]
74 Lepesheva GI,Virus C,Waterman MR.Conservation in the CYP51 family.Role of the B’helix/BC loop and helices F and Gin enzymatic function.Biochemistry 2003;42:9091-9101[PMID:12885242 DOI:10.1021/bi034663f]
75 Lepesheva GI,Zaitseva NG,Nes WD,Zhou W,Arase M,Liu J,Hill GC,Waterman MR.CYP51 from Trypanosoma cruzi:a phylaspecific residue in the B’helix defines substrate preferences of sterol 14alpha-demethylase.J Biol Chem 2006;281:3577-3585[PMID:16321980 DOI:10.1074/jbc.M510317200]
76 Dias LC,Dessoy MA,Silva JJN,Thiemann OH,Oliva G,Andricopulo AD.Quimioterapia da doen?a de Chagas:estado da arte e perspectivas no desenvolvimento de novos fármacos.Quím Nova2009;32:2444-2457[DOI:10.1590/S0100-40422009000900038]
77 Villalta F,Dobish MC,Nde PN,Kleshchenko YY,Hargrove TY,Johnson CA,Waterman MR,Johnston JN,Lepesheva GI.VNIcures acute and chronic experimental Chagas disease.J Infect Dis2013;208:504-511[PMID:23372180 DOI:10.1093/infdis/jit042]
78 Mc Cabe RE,Remington JS,Araujo FG.Ketoconazole promotes parasitological cure of mice infected with Trypanosoma cruzi.Trans R Soc Trop Med Hyg 1987;81:613-615[PMID:3127963DOI:10.1016/0035-9203(87)90430-5]
79 Pfaller MA,Krogstad DJ.Imidazole and polyene activity against chloroquine-resistant Plasmodium falciparum.J Infect Dis 1981;144:372-375[PMID:6270216 DOI:10.1093/infdis/144.4.372]
80 Berman JD.Activity of imidazoles against Leishmania tropica in human macrophage cultures.Am J Trop Med Hyg 1981;30:566-569[PMID:6266261]
81 Urbina JA.Ergosterol biosynthesis and drug development for Chagas disease.Mem Inst Oswaldo Cruz 2009;104 Suppl 1:311-318[PMID:19753490 DOI:10.1590/S0074-02762009000900041]
82 Shapiro RS,Robbins N,Cowen LE.Regulatory circuitry governing fungal development,drug resistance,and disease.Microbiol Mol Biol Rev 2011;75:213-267[PMID:21646428]
83 Abe F,Usui K,Hiraki T.Fluconazole modulates membrane rigidity,heterogeneity,and water penetration into the plasma membrane in Saccharomyces cerevisiae.Biochemistry 2009;48:8494-8504[PMID:19670905]
84 Franklim TN,Freire-de-Lima L,de Nazareth SáDiniz J,Previato JO,Castro RN,Mendon?a-Previato L,de Lima ME.Design,synthesis and trypanocidal evaluation of novel 1,2,4-triazoles-
3-thiones derived from natural piperine.Molecules 2013;18:6366-6382[PMID:23760033 DOI:10.3390/molecules18066366]
85 Warrilow AG,Parker JE,Kelly DE,Kelly SL.Azole affinity of sterol 14α-demethylase(CYP51)enzymes from Candida albicans and Homo sapiens.Antimicrob Agents Chemother 2013;57:1352-1360[PMID:23274672 DOI:10.1128/AAC.02067-12]
86 Conley A,Mapes S,Corbin CJ,Greger D,Walters K,Trant J,Graham S.A comparative approach to structure-function studies of mammalian aromatases.J Steroid Biochem Mol Biol 2001;79:289-297[PMID:11850235 DOI:10.1016/S0960-0760(01)00145-5]
87 Zarn JA,Brüschweiler BJ,Schlatter JR.Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14 alphademethylase and aromatase.Environ Health Perspect 2003;111:255-261[PMID:12611652 DOI:10.1289/ehp.5785]
88 Heald R,Nogales E.Microtubule dynamics.J Cell Sci 2002;115:3-4[PMID:11801717]
89 Westermann S,Weber K.Post-translational modifications regulate microtubule function.Nat Rev Mol Cell Biol 2003;4:938-947[PMID:14685172 DOI:10.1038/nrm1260]
90 Perez EA.Microtubule inhibitors:Differentiating tubulin-inhibiting agents based on mechanisms of action,clinical activity,and resistance.Mol Cancer Ther 2009;8:2086-2095[PMID:19671735 DOI:10.1158/1535-7163.MCT-09-0366]
91 Zhou J,Giannakakou P.Targeting microtubules for cancer chemotherapy.Curr Med Chem Anticancer Agents 2005;5:65-71[PMID:15720262 DOI:10.2174/1568011053352569]
92 Nogales E.Structural insight into microtubule function.Annu Rev Biophys Biomol Struct 2001;30:397-420[PMID:11441808 DOI:10.1146/annurev.biophys.30.1.397]
93 Akhmanova A,Steinmetz MO.Tracking the ends:a dynamic protein network controls the fate of microtubule tips.Nat Rev Mol Cell Biol 2008;9:309-322[PMID:18322465 DOI:10.1038/nrm2369]
94 Kuppens IE.Current state of the art of new tubulin inhibitors in the clinic.Curr Clin Pharmacol 2006;1:57-70[PMID:18666378DOI:10.2174/157488406775268200]
95 Werbovetz KA.Tubulin as an antiprotozoal drug target.Mini Rev Med Chem 2002;2:519-529[PMID:12370037 DOI:10.2174/1389557023405648]
96 Kilmartin JV.Purification of yeast tubulin by self-assembly in vitro.Biochemistry 1981;20:3629-3633[PMID:7020758 DOI:10.1021/bi00515a050]
97 Dawson PJ,Gutteridge WE,Gull K.A comparison of the interaction of anthelmintic benzimidazoles with tubulin isolated from mammalian tissue and the parasitic nematode Ascaridia galli.Biochem Pharmacol 1984;33:1069-1074[PMID:6712717 DOI:10.1016/0006-2952(84)90515-X]
98 Werbovetz KA,Sackett DL,Delfín D,Bhattacharya G,Salem M,Obrzut T,Rattendi D,Bacchi C.Selective antimicrotubule activity of N1-phenyl-3,5-dinitro-N4,N4-di-n-propylsulfanilamide(GB-II-5)against kinetoplastid parasites.Mol Pharmacol 2003;64:1325-1333[PMID:14645662 DOI:10.1124/mol.64.6.1325]
99 Zhong B,Cai X,Chennamaneni S,Yi X,Liu L,Pink JJ,Dowlati A,Xu Y,Zhou A,Su B.From COX-2 inhibitor nimesulide to potent anti-cancer agent:synthesis,in vitro,in vivo and pharmacokinetic evaluation.Eur J Med Chem 2012;47:432-444[PMID:22119125DOI:10.1016/j.ejmech.2011.11.012]
100 Lu Y,Chen J,Xiao M,Li W,Miller DD.An overview of tubulin inhibitors that interact with the colchicine binding site.Pharm Res2012;29:2943-2971[PMID:22814904 DOI:10.1007/s11095-012-0828-z]
101 Ravelli RB,Gigant B,Curmi PA,Jourdain I,Lachkar S,Sobel A,Knossow M.Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain.Nature 2004;428:198-202[PMID:15014504 DOI:10.1038/nature02393]
102 Cormier A,Knossow M,Wang C,Gigant B.The binding of vinca domain agents to tubulin:structural and biochemical studies.Methods Cell Biol 2010;95:373-390[PMID:20466145 DOI:10.1016/S0091-679X(10)95020-6]
103 Noble RL.The discovery of the vinca alkaloids--chemotherapeutic agents against cancer.Biochem Cell Biol 1990;68:1344-1351[PMID:2085431 DOI:10.1139/o90-197]
104 Sottomayor M,López-Serrano M,Di Cosmo F,Ros BarcelóA.Purification and characterization of alpha-3’,4’-anhydrovinblastine synthase(peroxidase-like)from Catharanthus roseus(L.)G.Don.FEBS Lett 1998;428:299-303[PMID:9654153 DOI:10.1016/S0014-5793(98)00551-1]
105 Almagro L,Fernández-Pérez F,Pedre?o MA.Indole alkaloids from Catharanthus roseus:bioproduction and their effect on human health.Molecules 2015;20:2973-3000[PMID:25685907 DOI:10.3390/molecules20022973]
106 Brand?o HN,David JP,Couto RD,Nascimento JAP,David JM.Química e farmacologia dos quimioterápicos antineoplásicos derivados de plantas.Quím Nova 2010;33:1359-1369[DOI:10.1590/S0100-40422010000600026]
107 Panda D,Jordan MA,Chu KC,Wilson L.Differential effects of vinblastine on polymerization and dynamics at opposite microtubule ends.J Biol Chem 1996;271:29807-29812[PMID:8939919 DOI:10.1074/jbc.271.47.29807]
108 Yang H,Ganguly A,Cabral F.Inhibition of cell migration and cell division correlates with distinct effects of microtubule inhibiting drugs.J Biol Chem 2010;285:32242-32250[PMID:20696757DOI:10.1074/jbc.M110.160820]
109 Amos LA,L?we J.How Taxol stabilises microtubule structure.Chem Biol 1999;6:R65-R69[PMID:10074470 DOI:10.1016/S1074-5521(99)89002-4]
110 Ojima I,Habus I,Zhao M,Zucco M,Park YH,Sun CM,Brigaud T.New and eficient approaches to the semisynthesis of taxol and its C-13 side chain analogs by means ofβ-lactam synthon method.Tetrahedron 1992;48:6985-7012[DOI:10.1016/S0040-4020(01)91210-4]
111 Fu Y,Li S,Zu Y,Yang G,Yang Z,Luo M,Jiang S,Wink M,Efferth T.Medicinal chemistry of paclitaxel and its analogues.Curr Med Chem 2009;16:3966-3985[PMID:19747129 DOI:10.2174/092986709789352277]
112 Baum SG,Wittner M,Nadler JP,Horwitz SB,Dennis JE,Schiff PB,Tanowitz HB.Taxol,a microtubule stabilizing agent,blocks the replication of Trypanosoma cruzi.Proc Natl Acad Sci USA 1981;78:4571-4575[PMID:6117077 DOI:10.1073/pnas.78.7.4571]
113 Freire-de-Lima L,Ribeiro TS,Rocha GM,Brand?o BA,Romeiro A,Mendon?a-Previato L,Previato JO,de Lima ME,de Carvalho TM,Heise N.The toxic effects of piperine against Trypanosoma cruzi:ultrastructural alterations and reversible blockage of cytokinesis in epimastigote forms.Parasitol Res 2008;102:1059-1067[PMID:18224488 DOI:10.1007/s00436-008-0876-9]
114 Gupta KK,Bharne SS,Rathinasamy K,Naik NR,Panda D.Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding.FEBS J 2006;273:5320-5332[PMID:17069615 DOI:10.1111/j.1742-4658.2006.05525.x]
115 Banerjee M,Singh P,Panda D.Curcumin suppresses the dynamic instability of microtubules,activates the mitotic checkpoint and induces apoptosis in MCF-7 cells.FEBS J 2010;277:3437-3448[PMID:20646066]
116 Chakraborti S,Das L,Kapoor N,Das A,Dwivedi V,Poddar A,Chakraborti G,Janik M,Basu G,Panda D,Chakrabarti P,Surolia A,Bhattacharyya B.Curcumin recognizes a unique binding site of tubulin.J Med Chem 2011;54:6183-6196[PMID:21830815 DOI:10.1021/jm2004046]
117 Sueth-Santiago V,Moraes JB,Sobral Alves ES,Vannier-Santos MA,Freire-de-Lima CG,Castro RN,Mendes-Silva GP,Del Cistia CN,Magalh?es LG,Andricopulo AD,Sant Anna CM,Decoté-Ricardo D,Freire de Lima ME.The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi:Cytotoxicity,Ultrastructural Alterations and Molecular Modeling Studies.PLoSOne 2016;11:e0162926[PMID:27658305 DOI:10.1371/journal.pone.0162926]