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

Target-based Screening of the Chagas Box: Setting Up Enzymatic Assays to Discover Specific Inhibitors Across Bioactive Compounds

Author(s): Emir Salas-Sarduy, Gabriela T. Niemirowicz, Juan José Cazzulo and Vanina E. Alvarez*

Volume 26, Issue 36, 2019

Page: [6672 - 6686] Pages: 15

DOI: 10.2174/0929867326666190705160637

Price: $65

Abstract

Chagas disease is a neglected tropical illness caused by the protozoan parasite Trypanosoma cruzi. The disease is endemic in Latin America with about 6 million people infected and many more being at risk. Only two drugs are available for treatment, Nifurtimox and Benznidazole, but they have a number of side effects and are not effective in all cases. This makes urgently necessary the development of new drugs, more efficient, less toxic and affordable to the poor people, who are most of the infected population. In this review we will summarize the current strategies used for drug discovery considering drug repositioning, phenotyping screenings and target-based approaches. In addition, we will describe in detail the considerations for setting up robust enzymatic assays aimed at identifying and validating small molecule inhibitors in high throughput screenings.

Keywords: Chagas disease, tropical illness, protozoan parasite, Trypanosoma cruzi, Nifurtimox and Benznidazole, drug repositioning, phenotyping screenings.

« Previous
[1]
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]
[2]
World Health Organization. Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis. World Health Organ. Tech. Rep. Ser., 2012, (975), v-xii, 1- 100.
[PMID: 23484340]
[3]
Dias, J.C. Southern cone initiative for the elimination of domestic populations of triatoma infestans and the interruption of transfusional chagas disease. Historical aspects, present situation, and perspectives. Mem. Inst. Oswaldo Cruz, 2007, 102(Suppl. 1), 11-18.
[http://dx.doi.org/10.1590/S0074-02762007005000092] [PMID: 17891281]
[4]
Gurevitz, J.M.; Gaspe, M.S.; Enriquez, G.F.; Provecho, Y.M.; Kitron, U.; Gürtler, R.E. Intensified surveillance and insecticide-based control of the Chagas disease vector Triatoma infestans in the Argentinean Chaco. PLoS Negl. Trop. Dis., 2013, 7(4)e2158
[http://dx.doi.org/10.1371/journal.pntd.0002158] [PMID: 23593525]
[5]
Bern, C.; Kjos, S.; Yabsley, M.J.; Montgomery, S.P. Trypanosoma cruzi and Chagas’ Disease in the United States. Clin. Microbiol. Rev., 2011, 24(4), 655-681.
[http://dx.doi.org/10.1128/CMR.00005-11] [PMID: 21976603]
[6]
Pérez-Molina, J.A.; Norman, F.; López-Vélez, R. Chagas disease in non-endemic countries: epidemiology, clinical presentation and treatment. Curr. Infect. Dis. Rep., 2012, 14(3), 263-274.
[http://dx.doi.org/10.1007/s11908-012-0259-3] [PMID: 22477037]
[7]
Requena-Méndez, A.; Aldasoro, E.; de Lazzari, E.; Sicuri, E.; Brown, M.; Moore, D.A.; Gascon, J.; Muñoz, J. Prevalence of Chagas disease in Latin-American migrants living in Europe: a systematic review and meta-analysis. PLoS Negl. Trop. Dis., 2015, 9(2)e0003540
[http://dx.doi.org/10.1371/journal.pntd.0003540] [PMID: 25680190]
[8]
Schijman, A.G.; Altcheh, J.; Burgos, J.M.; Biancardi, M.; Bisio, M.; Levin, M.J.; Freilij, H. Aetiological treatment of congenital Chagas’ disease diagnosed and monitored by the polymerase chain reaction. J. Antimicrob. Chemother., 2003, 52(3), 441-449.
[http://dx.doi.org/10.1093/jac/dkg338] [PMID: 12917253]
[9]
Morillo, C.A.; Marin-Neto, J.A.; Avezum, A.; Sosa-Estani, S.; Rassi, A., Jr; Rosas, F.; Villena, E.; Quiroz, R.; Bonilla, R.; Britto, C.; Guhl, F.; Velazquez, E.; Bonilla, L.; Meeks, B.; Rao-Melacini, P.; Pogue, J.; Mattos, A.; Lazdins, J.; Rassi, A.; Connolly, S.J.; Yusuf, S. BENEFIT Investigators. Randomized Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy. N. Engl. J. Med., 2015, 373(14), 1295-1306.
[http://dx.doi.org/10.1056/NEJMoa1507574] [PMID: 26323937]
[10]
Pecoul, B.; Batista, C.; Stobbaerts, E.; Ribeiro, I.; Vilasanjuan, R.; Gascon, J.; Pinazo, M.J.; Moriana, S.; Gold, S.; Pereiro, A.; Navarro, M.; Torrico, F.; Bottazzi, M.E.; Hotez, P.J. The BENEFIT Trial: Where Do We Go from Here? PLoS Negl. Trop. Dis., 2016, 10(2)e0004343
[http://dx.doi.org/10.1371/journal.pntd.0004343] [PMID: 26913759]
[11]
Don, R.; Ioset, J.R. Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections. Parasitology, 2014, 141(1), 140-146.
[http://dx.doi.org/10.1017/S003118201300142X] [PMID: 23985066]
[12]
Peña, I.; Pilar Manzano, M.; Cantizani, J.; Kessler, A.; Alonso-Padilla, J.; Bardera, A.I.; Alvarez, E.; Colmenarejo, G.; Cotillo, I.; Roquero, I.; de Dios-Anton, F.; Barroso, V.; Rodriguez, A.; Gray, D.W.; Navarro, M.; Kumar, V.; Sherstnev, A.; Drewry, D.H.; Brown, J.R.; Fiandor, J.M.; Julio Martin, J. New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource. Sci. Rep., 2015, 5, 8771.
[http://dx.doi.org/10.1038/srep08771] [PMID: 25740547]
[13]
Khare, S.; Nagle, A.S.; Biggart, A.; Lai, Y.H.; Liang, F.; Davis, L.C.; Barnes, S.W.; Mathison, C.J.; Myburgh, E.; Gao, M.Y.; Gillespie, J.R.; Liu, X.; Tan, J.L.; Stinson, M.; Rivera, I.C.; Ballard, J.; Yeh, V.; Groessl, T.; Federe, G.; Koh, H.X.; Venable, J.D.; Bursulaya, B.; Shapiro, M.; Mishra, P.K.; Spraggon, G.; Brock, A.; Mottram, J.C.; Buckner, F.S.; Rao, S.P.; Wen, B.G.; Walker, J.R.; Tuntland, T.; Molteni, V.; Glynne, R.J.; Supek, F. Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness. Nature, 2016, 537(7619), 229-233.
[http://dx.doi.org/10.1038/nature19339] [PMID: 27501246]
[14]
Engel, J.C.; Ang, K.K.; Chen, S.; Arkin, M.R.; McKerrow, J.H.; Doyle, P.S. Image-based high-throughput drug screening targeting the intracellular stage of Trypanosoma cruzi, the agent of Chagas’ disease. Antimicrob. Agents Chemother., 2010, 54(8), 3326-3334.
[http://dx.doi.org/10.1128/AAC.01777-09] [PMID: 20547819]
[15]
Berenstein, A.J.; Magariños, M.P.; Chernomoretz, A.; Agüero, F. A Multilayer network approach for guiding drug repositioning in neglected diseases. PLoS Negl. Trop. Dis., 2016, 10(1)e0004300
[http://dx.doi.org/10.1371/journal.pntd.0004300] [PMID: 26735851]
[16]
Urbina, J.A. Ergosterol biosynthesis and drug development for Chagas disease. Mem. Inst. Oswaldo Cruz, 2009, 104(Suppl. 1), 311-318.
[http://dx.doi.org/10.1590/S0074-02762009000900041] [PMID: 19753490]
[17]
Urbina, J.A.; Payares, G.; Contreras, L.M.; Liendo, A.; Sanoja, C.; Molina, J.; Piras, M.; Piras, R.; Perez, N.; Wincker, P.; Loebenberg, D. Antiproliferative effects and mechanism of action of SCH 56592 against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies. Antimicrob. Agents Chemother., 1998, 42(7), 1771-1777.
[http://dx.doi.org/10.1128/AAC.42.7.1771] [PMID: 9661019]
[18]
Molina, I.; Gómez i Prat, J.; Salvador, F.; Treviño, B.; Sulleiro, E.; Serre, N.; Pou, D.; Roure, S.; Cabezos, J.; Valerio, L.; Blanco-Grau, A.; Sánchez-Montalvá, A.; Vidal, X.; Pahissa, A. Randomized trial of posaconazole and benznidazole for chronic Chagas’ disease. N. Engl. J. Med., 2014, 370(20), 1899-1908.
[http://dx.doi.org/10.1056/NEJMoa1313122] [PMID: 24827034]
[19]
Francisco, A.F.; Lewis, M.D.; Jayawardhana, S.; Taylor, M.C.; Chatelain, E.; Kelly, J.M. Limited ability of posaconazole to cure both acute and chronic trypanosoma cruzi infections revealed by highly sensitive in vivo imaging. Antimicrob. Agents Chemother., 2015, 59(8), 4653-4661.
[http://dx.doi.org/10.1128/AAC.00520-15] [PMID: 26014936]
[20]
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: The STOP-CHAGAS trial. J. Am. Coll. Cardiol., 2017, 69(8), 939-947.
[http://dx.doi.org/10.1016/j.jacc.2016.12.023] [PMID: 28231946]
[21]
Nagle, A.S.; Khare, S.; Kumar, A.B.; Supek, F.; Buchynskyy, A.; Mathison, C.J.; Chennamaneni, N.K.; Pendem, N.; Buckner, F.S.; Gelb, M.H.; Molteni, V. Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis. Chem. Rev., 2014, 114(22), 11305-11347.
[http://dx.doi.org/10.1021/cr500365f] [PMID: 25365529]
[22]
Alonso-Padilla, J.; Rodríguez, A. High throughput screening for anti-Trypanosoma cruzi drug discovery. PLoS Negl. Trop. Dis., 2014, 8(12)e3259
[http://dx.doi.org/10.1371/journal.pntd.0003259] [PMID: 25474364]
[23]
Villarreal, D.; Barnabé, C.; Sereno, D.; Tibayrenc, M. Lack of correlation between in vitro susceptibility to Benznidazole and phylogenetic diversity of Trypanosoma cruzi, the agent of Chagas disease. Exp. Parasitol., 2004, 108(1-2), 24-31.
[http://dx.doi.org/10.1016/j.exppara.2004.07.001] [PMID: 15491545]
[24]
Mejia, A.M.; Hall, B.S.; Taylor, M.C.; Gómez-Palacio, A.; Wilkinson, S.R.; Triana-Chávez, O.; Kelly, J.M. Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population. J. Infect. Dis., 2012, 206(2), 220-228.
[http://dx.doi.org/10.1093/infdis/jis331] [PMID: 22551809]
[25]
Moraes, C.B.; Giardini, M.A.; Kim, H.; Franco, C.H.; Araujo-Junior, A.M.; Schenkman, S.; Chatelain, E.; Freitas-Junior, L.H. Nitroheterocyclic compounds are more efficacious than CYP51 inhibitors against Trypanosoma cruzi: implications for Chagas disease drug discovery and development. Sci. Rep., 2014, 4, 4703.
[http://dx.doi.org/10.1038/srep04703] [PMID: 24736467]
[26]
Sánchez-Valdéz, F.J.; Padilla, A.; Wang, W.; Orr, D.; Tarleton, R.L. Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure. eLife, 2018, 7pii e34039
[http://dx.doi.org/10.7554/eLife.34039] [PMID: 29578409]
[27]
MacLean, L.M.; Thomas, J.; Lewis, M.D.; Cotillo, I.; Gray, D.W.; De Rycker, M. Development of Trypanosoma cruzi in vitro assays to identify compounds suitable for progression in Chagas’ disease drug discovery. PLoS Negl. Trop. Dis., 2018, 12(7)e0006612
[http://dx.doi.org/10.1371/journal.pntd.0006612] [PMID: 30001347]
[28]
El-Sayed, N.M.; Myler, P.J.; Bartholomeu, D.C.; Nilsson, D.; Aggarwal, G.; Tran, A.N.; Ghedin, E.; Worthey, E.A.; Delcher, A.L.; Blandin, G.; Westenberger, S.J.; Caler, E.; Cerqueira, G.C.; Branche, C.; Haas, B.; Anupama, A.; Arner, E.; Aslund, L.; Attipoe, P.; Bontempi, E.; Bringaud, F.; Burton, P.; Cadag, E.; Campbell, D.A.; Carrington, M.; Crabtree, J.; Darban, H.; da Silveira, J.F.; de Jong, P.; Edwards, K.; Englund, P.T.; Fazelina, G.; Feldblyum, T.; Ferella, M.; Frasch, A.C.; Gull, K.; Horn, D.; Hou, L.; Huang, Y.; Kindlund, E.; Klingbeil, M.; Kluge, S.; Koo, H.; Lacerda, D.; Levin, M.J.; Lorenzi, H.; Louie, T.; Machado, C.R.; McCulloch, R.; McKenna, A.; Mizuno, Y.; Mottram, J.C.; Nelson, S.; Ochaya, S.; Osoegawa, K.; Pai, G.; Parsons, M.; Pentony, M.; Pettersson, U.; Pop, M.; Ramirez, J.L.; Rinta, J.; Robertson, L.; Salzberg, S.L.; Sanchez, D.O.; Seyler, A.; Sharma, R.; Shetty, J.; Simpson, A.J.; Sisk, E.; Tammi, M.T.; Tarleton, R.; Teixeira, S.; Van Aken, S.; Vogt, C.; Ward, P.N.; Wickstead, B.; Wortman, J.; White, O.; Fraser, C.M.; Stuart, K.D.; Andersson, B. The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science, 2005, 309(5733), 409-415.
[http://dx.doi.org/10.1126/science.1112631] [PMID: 16020725]
[29]
Reigada, C.; Valera-Vera, E.A.; Sayé, M.; Errasti, A.E.; Avila, C.C.; Miranda, M.R.; Pereira, C.A. Trypanocidal effect of isotretinoin through the inhibition of polyamine and amino acid transporters in trypanosoma cruzi. PLoS Negl. Trop. Dis., 2017, 11(3)e0005472
[http://dx.doi.org/10.1371/journal.pntd.0005472] [PMID: 28306713]
[30]
Alvarez, V.E.; Niemirowicz, G.T.; Cazzulo, J.J. The peptidases of Trypanosoma cruzi: digestive enzymes, virulence factors, and mediators of autophagy and programmed cell death. Biochim. Biophys. Acta, 2012, 1824(1), 195-206.
[http://dx.doi.org/10.1016/j.bbapap.2011.05.011] [PMID: 21621652]
[31]
Diaz-Gonzalez, R.; Kuhlmann, F.M.; Galan-Rodriguez, C.; Madeira da Silva, L.; Saldivia, M.; Karver, C.E.; Rodriguez, A.; Beverley, S.M.; Navarro, M.; Pollastri, M.P. The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors affords a new opportunity for drug repurposing. PLoS Negl. Trop. Dis., 2011, 5(8)e1297
[http://dx.doi.org/10.1371/journal.pntd.0001297] [PMID: 21886855]
[32]
Schoijet, A.C.; Miranda, K.; Medeiros, L.C.; de Souza, W.; Flawiá, M.M.; Torres, H.N.; Pignataro, O.P.; Docampo, R.; Alonso, G.D. Defining the role of a FYVE domain in the localization and activity of a cAMP phosphodiesterase implicated in osmoregulation in Trypanosoma cruzi. Mol. Microbiol., 2011, 79(1), 50-62.
[http://dx.doi.org/10.1111/j.1365-2958.2010.07429.x] [PMID: 21166893]
[33]
King-Keller, S.; Li, M.; Smith, A.; Zheng, S.; Kaur, G.; Yang, X.; Wang, B.; Docampo, R. Chemical validation of phosphodiesterase C as a chemotherapeutic target in Trypanosoma cruzi, the etiological agent of Chagas’ disease. Antimicrob. Agents Chemother., 2010, 54(9), 3738-3745.
[http://dx.doi.org/10.1128/AAC.00313-10] [PMID: 20625148]
[34]
Alonso, V.L.; Ritagliati, C.; Cribb, P.; Cricco, J.A.; Serra, E.C. Overexpression of bromodomain factor 3 in Trypanosoma cruzi (TcBDF3) affects differentiation of the parasite and protects it against bromodomain inhibitors. FEBS J., 2016, 283(11), 2051-2066.
[http://dx.doi.org/10.1111/febs.13719] [PMID: 27007774]
[35]
Moretti, N.S.; da Silva Augusto, L.; Clemente, T.M.; Antunes, R.P.; Yoshida, N.; Torrecilhas, A.C.; Cano, M.I.; Schenkman, S. Characterization of Trypanosoma cruzi Sirtuins as Possible Drug Targets for Chagas Disease. Antimicrob. Agents Chemother., 2015, 59(8), 4669-4679.
[http://dx.doi.org/10.1128/AAC.04694-14] [PMID: 26014945]
[36]
DaRocha, W.D.; Otsu, K.; Teixeira, S.M.; Donelson, J.E. Tests of cytoplasmic RNA interference (RNAi) and construction of a tetracycline-inducible T7 promoter system in Trypanosoma cruzi. Mol. Biochem. Parasitol., 2004, 133(2), 175-186.
[http://dx.doi.org/10.1016/j.molbiopara.2003.10.005] [PMID: 14698430]
[37]
Okura, M.; Fang, J.; Salto, M.L.; Singer, R.S.; Docampo, R.; Moreno, S.N. A lipid-modified phosphoinositide-specific phospholipase C (TcPI-PLC) is involved in differentiation of trypomastigotes to amastigotes of Trypanosoma cruzi. J. Biol. Chem., 2005, 280(16), 16235-16243.
[http://dx.doi.org/10.1074/jbc.M414535200] [PMID: 15710612]
[38]
Málaga, S.; Yoshida, N. Targeted reduction in expression of Trypanosoma cruzi surface glycoprotein gp90 increases parasite infectivity. Infect. Immun., 2001, 69(1), 353-359.
[http://dx.doi.org/10.1128/IAI.69.1.353-359.2001] [PMID: 11119524]
[39]
Araya, J.E.; Cornejo, A.; Orrego, P.R.; Cordero, E.M.; Cortéz, M.; Olivares, H.; Neira, I.; Sagua, H.; da Silveira, J.F.; Yoshida, N.; González, J. Calcineurin B of the human protozoan parasite Trypanosoma cruzi is involved in cell invasion. Microbes Infect., 2008, 10(8), 892-900.
[http://dx.doi.org/10.1016/j.micinf.2008.05.003] [PMID: 18657458]
[40]
Hashimoto, M.; Nara, T.; Hirawake, H.; Morales, J.; Enomoto, M.; Mikoshiba, K. Antisense oligonucleotides targeting parasite inositol 1,4,5-trisphosphate receptor inhibits mammalian host cell invasion by Trypanosoma cruzi. Sci. Rep., 2014, 4, 4231.
[http://dx.doi.org/10.1038/srep04231] [PMID: 24577136]
[41]
Taylor, M.C.; Huang, H.; Kelly, J.M. Genetic techniques in Trypanosoma cruzi. Adv. Parasitol., 2011, 75, 231-250.
[http://dx.doi.org/10.1016/B978-0-12-385863-4.00011-3] [PMID: 21820559]
[42]
Obado, S.O.; Taylor, M.C.; Wilkinson, S.R.; Bromley, E.V.; Kelly, J.M. Functional mapping of a trypanosome centromere by chromosome fragmentation identifies a 16-kb GC-rich transcriptional “strand-switch” domain as a major feature. Genome Res., 2005, 15(1), 36-43.
[http://dx.doi.org/10.1101/gr.2895105] [PMID: 15632088]
[43]
Minning, T.A.; Weatherly, D.B.; Atwood, J., III; Orlando, R.; Tarleton, R.L. The steady-state transcriptome of the four major life-cycle stages of Trypanosoma cruzi. BMC Genomics, 2009, 10, 370.
[http://dx.doi.org/10.1186/1471-2164-10-370] [PMID: 19664227]
[44]
Peng, D.; Kurup, S.P.; Yao, P.Y.; Minning, T.A.; Tarleton, R.L. CRISPR-Cas9-mediated single-gene and gene family disruption in Trypanosoma cruzi. MBio, 2014, 6(1), e02097-e14.
[http://dx.doi.org/10.1128/mBio.02097-14] [PMID: 25550322]
[45]
Lander, N.; Li, Z.H.; Niyogi, S.; Docampo, R. CRISPR/Cas9-induced disruption of paraflagellar rod protein 1 and 2 genes in trypanosoma cruzi reveals their role in flagellar attachment. MBio, 2015, 6(4)e01012
[http://dx.doi.org/10.1128/mBio.01012-15] [PMID: 26199333]
[46]
Soares Medeiros, L.C.; South, L.; Peng, D.; Bustamante, J.M.; Wang, W.; Bunkofske, M.; Perumal, N.; Sanchez-Valdez, F.; Tarleton, R.L. Rapid, selection-free, high-efficiency genome editing in protozoan parasites using crispr-cas9 ribonucleoproteins. MBio, 2017, 8(6), e01788-e17.
[http://dx.doi.org/10.1128/mBio.01788-17] [PMID: 29114029]
[47]
Romagnoli, B.A.A.; Picchi, G.F.A.; Hiraiwa, P.M.; Borges, B.S.; Alves, L.R.; Goldenberg, S. Improvements in the CRISPR/Cas9 system for high efficiency gene disruption in Trypanosoma cruzi. Acta Trop., 2018, 178, 190-195.
[http://dx.doi.org/10.1016/j.actatropica.2017.11.013] [PMID: 29174293]
[48]
Salas-Sarduy, E.; Landaburu, L.U.; Karpiak, J.; Madauss, K.P.; Cazzulo, J.J.; Agüero, F.; Alvarez, V.E. Novel scaffolds for inhibition of Cruzipain identified from high-throughput screening of anti-kinetoplastid chemical boxes. Sci. Rep., 2017, 7(1), 12073.
[http://dx.doi.org/10.1038/s41598-017-12170-4] [PMID: 28935948]
[49]
Entzeroth, M.; Flotow, H.; Condron, P. Overview of highthroughput screening. Curr Protoc Pharmacol, , 2009, Chapter 9, Unit 9.4.
[http://dx.doi.org/10.1002/0471141755.ph0904s44] [PMID: 22294406]
[50]
Crowther, G.J.; Hillesland, H.K.; Keyloun, K.R.; Reid, M.C.; Lafuente-Monasterio, M.J.; Ghidelli-Disse, S.; Leonard, S.E.; He, P.; Jones, J.C.; Krahn, M.M.; Mo, J.S.; Dasari, K.S.; Fox, A.M.; Boesche, M.; El Bakkouri, M.; Rivas, K.L.; Leroy, D.; Hui, R.; Drewes, G.; Maly, D.J.; Van Voorhis, W.C.; Ojo, K.K. Biochemical screening of five protein kinases from plasmodium falciparum against 14,000 cell-active compounds. PLoS One, 2016, 11(3)e0149996
[http://dx.doi.org/10.1371/journal.pone.0149996] [PMID: 26934697]
[51]
Kaiser, M.; Maes, L.; Tadoori, L.P.; Spangenberg, T.; Ioset, J.R. Repurposing of the open access malaria box for kinetoplastid diseases identifies novel active scaffolds against trypanosomatids. J. Biomol. Screen., 2015, 20(5), 634-645.
[http://dx.doi.org/10.1177/1087057115569155] [PMID: 25690568]
[52]
Spalenka, J.; Escotte-Binet, S.; Bakiri, A.; Hubert, J.; Renault, J.H.; Velard, F.; Duchateau, S.; Aubert, D.; Huguenin, A.; Villena, I. Discovery of new inhibitors of toxoplasma gondii via the pathogen box. Antimicrob. Agents Chemother., 2018, 62(2), e01640-e17.
[http://dx.doi.org/10.1128/AAC.01640-17] [PMID: 29133550]
[53]
Gribbon, P.; Sewing, A. Fluorescence readouts in HTS: no gain without pain? Drug Discov. Today, 2003, 8(22), 1035-1043.
[http://dx.doi.org/10.1016/S1359-6446(03)02895-2] [PMID: 14690634]
[54]
Thorne, N.; Auld, D.S.; Inglese, J. Apparent activity in high-throughput screening: origins of compound-dependent assay interference. Curr. Opin. Chem. Biol., 2010, 14(3), 315-324.
[http://dx.doi.org/10.1016/j.cbpa.2010.03.020] [PMID: 20417149]
[55]
Simeonov, A.; Jadhav, A.; Thomas, C.J.; Wang, Y.; Huang, R.; Southall, N.T.; Shinn, P.; Smith, J.; Austin, C.P.; Auld, D.S.; Inglese, J. Fluorescence spectroscopic profiling of compound libraries. J. Med. Chem., 2008, 51(8), 2363-2371.
[http://dx.doi.org/10.1021/jm701301m] [PMID: 18363325]
[56]
Palmier, M.O.; Van Doren, S.R. Rapid determination of enzyme kinetics from fluorescence: overcoming the inner filter effect. Anal. Biochem., 2007, 371(1), 43-51.
[http://dx.doi.org/10.1016/j.ab.2007.07.008] [PMID: 17706587]
[57]
Jadhav, A.; Ferreira, R.S.; Klumpp, C.; Mott, B.T.; Austin, C.P.; Inglese, J.; Thomas, C.J.; Maloney, D.J.; Shoichet, B.K.; Simeonov, A. Quantitative analyses of aggregation, autofluorescence, and reactivity artifacts in a screen for inhibitors of a thiol protease. J. Med. Chem., 2010, 53(1), 37-51.
[http://dx.doi.org/10.1021/jm901070c] [PMID: 19908840]
[58]
Ryan, A.J.; Gray, N.M.; Lowe, P.N.; Chung, C.W. Effect of detergent on “promiscuous” inhibitors. J. Med. Chem., 2003, 46(16), 3448-3451.
[http://dx.doi.org/10.1021/jm0340896] [PMID: 12877581]
[59]
Klumpp, M. Non-stoichiometric inhibition in integrated lead finding - a literature review. Expert Opin. Drug Discov., 2016, 11(2), 149-162.
[http://dx.doi.org/10.1517/17460441.2016.1128892] [PMID: 26653534]
[60]
Feng, B.Y.; Shoichet, B.K. A detergent-based assay for the detection of promiscuous inhibitors. Nat. Protoc., 2006, 1(2), 550-553.
[http://dx.doi.org/10.1038/nprot.2006.77] [PMID: 17191086]
[61]
Arkin, M.; Auld, D.; Baell, J.; Brimacombe, K.; Dahlin, J.L.; Foley, T.L.; Inglese, J.; Kales, S.C. Assay artifacts and interferences. In: Assay guidance manual [Internet], Sittampalam, G.S.; Gal-Edd, N.; Arkin, M.; Auld, D.; Austin, C.; Bejcek, B.; Glicksman, M.; Inglese, J.; Lemmon, V.; Li, Z.; McGee, J.; McManus, O.; Minor, L.; Napper, A.; Riss, T.; Trask, Jr.O.J.; Weidner, J. (ed.). Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences. 2004.
[PMID: 22553861]
[62]
Zhang, J.H.; Chung, T.D.; Oldenburg, K.R. A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J. Biomol. Screen., 1999, 4(2), 67-73.
[http://dx.doi.org/10.1177/108705719900400206] [PMID: 10838414]
[63]
Williams, J.W.; Morrison, J.F. The kinetics of reversible tight-binding inhibition. Methods Enzymol., 1979, 63, 437-467.
[http://dx.doi.org/10.1016/0076-6879(79)63019-7] [PMID: 502865]
[64]
Copeland, R.A. Evaluation of enzyme inhibitors in drug discovery. A guide for medicinal chemists and pharmacologists. Methods Biochem. Anal., 2005, 46, 1-265.
[PMID: 16350889]
[65]
Copeland, R.A. Mechanistic considerations in high-throughput screening. Anal. Biochem., 2003, 320(1), 1-12.
[http://dx.doi.org/10.1016/S0003-2697(03)00346-4] [PMID: 12895464]
[66]
Yang, J.; Copeland, R.A.; Lai, Z. Defining balanced conditions for inhibitor screening assays that target bisubstrate enzymes. J. Biomol. Screen., 2009, 14(2), 111-120.
[http://dx.doi.org/10.1177/1087057108328763] [PMID: 19196704]
[67]
Malo, N.; Hanley, J.A.; Cerquozzi, S.; Pelletier, J.; Nadon, R. Statistical practice in high-throughput screening data analysis. Nat. Biotechnol., 2006, 24(2), 167-175.
[http://dx.doi.org/10.1038/nbt1186] [PMID: 16465162]
[68]
Habig, M.; Blechschmidt, A.; Dressler, S.; Hess, B.; Patel, V.; Billich, A.; Ostermeier, C.; Beer, D.; Klumpp, M. Efficient elimination of nonstoichiometric enzyme inhibitors from HTS hit lists. J. Biomol. Screen., 2009, 14(6), 679-689.
[http://dx.doi.org/10.1177/1087057109336586] [PMID: 19470716]
[69]
Caffrey, C.R.; Lima, A.P.; Steverding, D. Cysteine peptidases of kinetoplastid parasites. Adv. Exp. Med. Biol., 2011, 712, 84-99.
[http://dx.doi.org/10.1007/978-1-4419-8414-2_6] [PMID: 21660660]
[70]
Cazzulo, J.J.; Cazzulo Franke, M.C.; Martínez, J.; Franke de Cazzulo, B.M. Some kinetic properties of a cysteine proteinase (cruzipain) from Trypanosoma cruzi. Biochim. Biophys. Acta, 1990, 1037(2), 186-191.
[http://dx.doi.org/10.1016/0167-4838(90)90166-D] [PMID: 2407295]
[71]
Campetella, O.; Henriksson, J.; Aslund, L.; Frasch, A.C.; Pettersson, U.; Cazzulo, J.J. The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is encoded by multiple polymorphic tandemly organized genes located on different chromosomes. Mol. Biochem. Parasitol., 1992, 50(2), 225-234.
[http://dx.doi.org/10.1016/0166-6851(92)90219-A] [PMID: 1311053]
[72]
Campetella, O.; Martínez, J.; Cazzulo, J.J. A major cysteine proteinase is developmentally regulated in Trypanosoma cruzi. FEMS Microbiol. Lett., 1990, 55(1-2), 145-149.
[http://dx.doi.org/10.1111/j.1574-6968.1990.tb13852.x] [PMID: 2184087]
[73]
Jose Cazzulo, J.; Stoka, V.; Turk, V. The major cysteine proteinase of Trypanosoma cruzi: a valid target for chemotherapy of Chagas disease. Curr. Pharm. Des., 2001, 7(12), 1143-1156.
[http://dx.doi.org/10.2174/1381612013397528] [PMID: 11472258]
[74]
McKerrow, J.H.; Caffrey, C.; Kelly, B.; Loke, P.; Sajid, M. Proteases in parasitic diseases. Annu. Rev. Pathol., 2006, 1, 497-536.
[http://dx.doi.org/10.1146/annurev.pathol.1.110304.100151] [PMID: 18039124]
[75]
Franke de Cazzulo, B.M.; Martínez, J.; North, M.J.; Coombs, G.H.; Cazzulo, J.J. Effects of proteinase inhibitors on the growth and differentiation of Trypanosoma cruzi. FEMS Microbiol. Lett., 1994, 124(1), 81-86.
[http://dx.doi.org/10.1111/j.1574-6968.1994.tb07265.x] [PMID: 8001773]
[76]
Tomas, A.M.; Miles, M.A.; Kelly, J.M. Overexpression of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, is associated with enhanced metacyclogenesis. Eur. J. Biochem., 1997, 244(2), 596-603.
[http://dx.doi.org/10.1111/j.1432-1033.1997.t01-1-00596.x] [PMID: 9119029]
[77]
Harth, G.; Andrews, N.; Mills, A.A.; Engel, J.C.; Smith, R.; McKerrow, J.H. Peptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi. Mol. Biochem. Parasitol., 1993, 58(1), 17-24.
[http://dx.doi.org/10.1016/0166-6851(93)90086-D] [PMID: 8459830]
[78]
Meirelles, M.N.; Juliano, L.; Carmona, E.; Silva, S.G.; Costa, E.M.; Murta, A.C.; Scharfstein, J. Inhibitors of the major cysteinyl proteinase (GP57/51) impair host cell invasion and arrest the intracellular development of Trypanosoma cruzi in vitro. Mol. Biochem. Parasitol., 1992, 52(2), 175-184.
[http://dx.doi.org/10.1016/0166-6851(92)90050-T] [PMID: 1620157]
[79]
Ashall, F.; Angliker, H.; Shaw, E. Lysis of trypanosomes by peptidyl fluoromethyl ketones. Biochem. Biophys. Res. Commun., 1990, 170(2), 923-929.
[http://dx.doi.org/10.1016/0006-291X(90)92179-4] [PMID: 2116800]
[80]
Engel, J.C.; Doyle, P.S.; Hsieh, I.; McKerrow, J.H. Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J. Exp. Med., 1998, 188(4), 725-734.
[http://dx.doi.org/10.1084/jem.188.4.725] [PMID: 9705954]
[81]
Doyle, P.S.; Zhou, Y.M.; Engel, J.C.; McKerrow, J.H. A cysteine protease inhibitor cures Chagas’ disease in an immunodeficient-mouse model of infection. Antimicrob. Agents Chemother., 2007, 51(11), 3932-3939.
[http://dx.doi.org/10.1128/AAC.00436-07] [PMID: 17698625]
[82]
Barr, S.C.; Warner, K.L.; Kornreic, B.G.; Piscitelli, J.; Wolfe, A.; Benet, L.; McKerrow, J.H. A cysteine protease inhibitor protects dogs from cardiac damage during infection by Trypanosoma cruzi. Antimicrob. Agents Chemother., 2005, 49(12), 5160-5161.
[http://dx.doi.org/10.1128/AAC.49.12.5160-5161.2005] [PMID: 16304193]
[83]
Ferreira, R.S.; Simeonov, A.; Jadhav, A.; Eidam, O.; Mott, B.T.; Keiser, M.J.; McKerrow, J.H.; Maloney, D.J.; Irwin, J.J.; Shoichet, B.K. Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors. J. Med. Chem., 2010, 53(13), 4891-4905.
[http://dx.doi.org/10.1021/jm100488w] [PMID: 20540517]
[84]
Cazzulo, J.J.; Martínez, J.; Parodi, A.J.; Wernstedt, C.; Hellman, U. On the post-translational modifications at the C-terminal domain of the major cysteine proteinase (cruzipain) from Trypanosoma cruzi. FEMS Microbiol. Lett., 1992, 100(1-3), 411-416.
[http://dx.doi.org/10.1111/j.1574-6968.1992.tb05733.x] [PMID: 1478474]
[85]
Selwyn, M.J. A simple test for inactivation of an enzyme during assay. Biochim. Biophys. Acta, 1965, 105(1), 193-195.
[http://dx.doi.org/10.1016/S0926-6593(65)80190-4] [PMID: 4221326]
[86]
Feng, B.Y.; Simeonov, A.; Jadhav, A.; Babaoglu, K.; Inglese, J.; Shoichet, B.K.; Austin, C.P. A high-throughput screen for aggregation-based inhibition in a large compound library. J. Med. Chem., 2007, 50(10), 2385-2390.
[http://dx.doi.org/10.1021/jm061317y] [PMID: 17447748]
[87]
Johnston, P.A.; Soares, K.M.; Shinde, S.N.; Foster, C.A.; Shun, T.Y.; Takyi, H.K.; Wipf, P.; Lazo, J.S. Development of a 384-well colorimetric assay to quantify hydrogen peroxide generated by the redox cycling of compounds in the presence of reducing agents. Assay Drug Dev. Technol., 2008, 6(4), 505-518.
[http://dx.doi.org/10.1089/adt.2008.151] [PMID: 18699726]
[88]
Soares, K.M.; Blackmon, N.; Shun, T.Y.; Shinde, S.N.; Takyi, H.K.; Wipf, P.; Lazo, J.S.; Johnston, P.A. Profiling the NIH Small Molecule Repository for compounds that generate H2O2 by redox cycling in reducing environments. Assay Drug Dev. Technol., 2010, 8(2), 152-174.
[http://dx.doi.org/10.1089/adt.2009.0247] [PMID: 20070233]
[89]
Smith, G.K.; Barrett, D.G.; Blackburn, K.; Cory, M.; Dallas, W.S.; Davis, R.; Hassler, D.; McConnell, R.; Moyer, M.; Weaver, K. Expression, preparation, and high-throughput screening of caspase-8: discovery of redox-based and steroid diacid inhibition. Arch. Biochem. Biophys., 2002, 399(2), 195-205.
[http://dx.doi.org/10.1006/abbi.2002.2757] [PMID: 11888206]

Rights & Permissions Print Cite
Article Metrics
38
2
World Chagas Disease
© 2024 Bentham Science Publishers | Privacy Policy