In vitro and in vivo high-throughput assays for the testing of anti-Trypanosoma cruzi compounds.

PLoS Neglected Tropical Diseases
Adriana M C CanavaciRick L Tarleton

Abstract

The two available drugs for treatment of T. cruzi infection, nifurtimox and benznidazole (BZ), have potential toxic side effects and variable efficacy, contributing to their low rate of use. With scant economic resources available for antiparasitic drug discovery and development, inexpensive, high-throughput and in vivo assays to screen potential new drugs and existing compound libraries are essential. In this work, we describe the development and validation of improved methods to test anti-T. cruzi compounds in vitro and in vivo using parasite lines expressing the firefly luciferase (luc) or the tandem tomato fluorescent protein (tdTomato). For in vitro assays, the change in fluorescence intensity of tdTomato-expressing lines was measured as an indicator of parasite replication daily for 4 days and this method was used to identify compounds with IC(50) lower than that of BZ. This method was highly reproducible and had the added advantage of requiring relatively low numbers of parasites and no additional indicator reagents, enzymatic post-processes or laborious visual counting. In vivo, mice were infected in the footpads with fluorescent or bioluminescent parasites and the signal intensity was measured as a surrogate of parasit...Continue Reading

References

Oct 1, 1994·Memórias do Instituto Oswaldo Cruz·A C La FlammeW C Van Voorhis
Aug 26, 1998·The Journal of Experimental Medicine·J C EngelJ H McKerrow
Nov 24, 1998·Histochemistry and Cell Biology·S C BourguignonT Souto-Padrón
Jun 6, 2000·The Journal of Antimicrobial Chemotherapy·M S AraújoZ Brener
Aug 30, 2000·Cell Motility and the Cytoskeleton·K M Tyler, D M Engman
Jan 2, 2001·Parasitology Research·S Muelas-SerranoA Gómez-Barrio
Apr 4, 2001·Memórias do Instituto Oswaldo Cruz·R A Martínez-DíazA Gómez-Barrio
May 7, 2002·Memórias do Instituto Oswaldo Cruz·José Rodriques Coura, Solange L de Castro
Sep 28, 2002·The Biochemical Journal·Arkady F FradkovKonstantin A Lukyanov
May 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yan FengTomas Kirchhausen
May 29, 2003·Combinatorial Chemistry & High Throughput Screening·J C YarrowT J Mitchison
Jun 13, 2003·Gene·Hernán Alejandro LorenziMariano Jorge Levin
Oct 29, 2003·Trends in Parasitology·Julio A Urbina, Roberto Docampo
Nov 25, 2003·Parasitology Research·Wanderson D DaRochaSantuza M R Teixeira
Jan 28, 2005·Archiv der Pharmazie·Vladimir V KouznetsovJuan Amaro-Luis
Oct 13, 2006·Neoplasia : an International Journal for Oncology Research·Paul T WinnardVenu Raman
Oct 20, 2006·Trends in Parasitology·Chris J SchofieldRoberto Salvatella
Oct 21, 2006·Parasitology Research·Juliana SaraivaSérgio de Albuquerque
Nov 15, 2007·JAMA : the Journal of the American Medical Association·Caryn BernAnne C Moore
Dec 29, 2007·PLoS Medicine·Rick L TarletonRicardo E Gürtler
Jan 15, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Vijayalakshmi Nagappan, Stan Deresinski
Mar 4, 2008·Biological & Pharmaceutical Bulletin·João Marcos BatistaMaysa Furlan
May 31, 2008·International Journal for Parasitology·Kenneth V HylandDavid M Engman
Aug 23, 2008·Immunity·Tatyana ChtanovaEllen A Robey
Sep 10, 2008·Natural Product Research·Adriana Aparecida LopesMaysa Furlan
Jan 16, 2009·Bioorganic & Medicinal Chemistry Letters·João NeresKenneth T Douglas
Mar 4, 2009·Expert Review of Anti-infective Therapy·Rodolfo ViottiAlejandro Armenti
Apr 16, 2009·BMJ : British Medical Journal·Richard ReithingerRicardo E Gürtler
May 13, 2009·BMC Microbiology·Dan XuRick L Tarleton
Dec 8, 2009·Bioorganic & Medicinal Chemistry Letters·José C AponteMichel Sauvain
Apr 2, 2010·Bioorganic & Medicinal Chemistry·José C AponteGerald B Hammond

❮ Previous
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Citations

Mar 5, 2014·Parasites & Vectors·Cristina HenriquesWanderley de Souza
Jul 11, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·F M FrankL V Muschietti
Oct 23, 2013·Future Medicinal Chemistry·Maria V PapadopoulouAna Rodriguez
Sep 14, 2011·PLoS Neglected Tropical Diseases·Grasiella AndrianiAna Rodriguez
Oct 26, 2011·Journal of Medicinal Chemistry·Maria V PapadopoulouEls Torreele
Sep 28, 2012·Parasites & Vectors·Cristina HenriquesWanderley de Souza
Oct 5, 2013·European Journal of Medicinal Chemistry·Pablo D ElicioJuan B Rodriguez
Aug 16, 2013·The Journal of Infectious Diseases·Juan M BustamanteRick L Tarleton
Aug 18, 2012·Transactions of the Royal Society of Tropical Medicine and Hygiene·M G AlvarezR Viotti
Feb 12, 2013·Bioinformatics·Douglas E V PiresWagner Meira
Jul 17, 2013·Parasites & Vectors·Nick Van ReetPhilippe Büscher
Dec 17, 2014·Expert Review of Vaccines·Fernando J Sánchez-ValdézMiguel Ángel Basombrío
Apr 11, 2014·Expert Review of Clinical Pharmacology·Juan M Bustamante, Rick L Tarleton
Jun 30, 2011·Expert Opinion on Drug Discovery·Juan M Bustamante, Rick L Tarleton
Jun 1, 2012·Expert Opinion on Drug Discovery·Juan M BustamanteUNKNOWN The Chagas Drug Discovery Consortium
Jan 16, 2013·European Journal of Medicinal Chemistry·Marion RecherJuan B Rodriguez
Jan 14, 2016·The New England Journal of Medicine·Carlos A MorilloAlvaro Avezum
Jan 27, 2012·Trends in Parasitology·Ana Rodriguez, Rick L Tarleton
Apr 2, 2010·Bioorganic & Medicinal Chemistry·José C AponteGerald B Hammond
Sep 27, 2014·Drug Discovery Today·Estefanía Calvo-ÁlvarezRosa M Reguera
Jun 19, 2012·Bioengineered·Cecilia Pérez Brandan, Miguel Ángel Basombrío
Dec 5, 2014·PLoS Neglected Tropical Diseases·Julio Alonso-Padilla, Ana Rodríguez
Feb 28, 2017·Nature Reviews. Microbiology·Mark C FieldIan H Gilbert
May 7, 2015·Memórias do Instituto Oswaldo Cruz·Maria-Jesus PinazoJoaquim Gascon
Oct 16, 2014·Memórias do Instituto Oswaldo Cruz·Bianca ZingalesUNKNOWN Chagas Clinical Research Platform Meeting
Nov 26, 2015·The American Journal of Tropical Medicine and Hygiene·Sarah M GunterEric L Brown
Mar 27, 2018·ELife·Fernando J Sánchez-ValdézRick L Tarleton
Aug 12, 2015·Archives of Pharmacal Research·Michelle Lay Teng AngKevin Pethe
Sep 6, 2018·PloS One·Luz P Quebrada PalacioMiriam Postan
Aug 17, 2018·Expert Review of Clinical Pharmacology·Jadel Müller KratzSergio Sosa-Estani
Feb 22, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Bruno DemoroLucía Otero
Oct 5, 2014·Journal of Biomolecular Screening·R Jeffrey NeitzJair L Siqueira-Neto

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Methods Mentioned

BETA
flow cytometry
PCR
imaging technique

Software Mentioned

GraphPad PRISM
Image
Maestro
FlowJo
Living

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