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Prodrugs as new therapies against Chagas disease: in vivo synergy between Trypanosoma cruziproline racemase inhibitors and benznidazole

Authors :
de Melo, Guilherme Dias
Coatnoan, Nicolas
Gouault, Nicolas
Cupif, Jean-François
Renault, Jacques
Cosson, Alain
Uriac, Philippe
Blondel, Arnaud
Minoprio, Paola
Source :
Journal of Global Antimicrobial Resistance; March 2022, Vol. 28 Issue: 1 p84-89, 6p
Publication Year :
2022

Abstract

•Our novel compounds specifically inhibit T. cruziproline racemase (TcPRAC).•They covalently bind to TcPRAC in biochemical assays.•The corresponding ester prodrugs are effective at killing parasites in vitro.•JR1531 prodrug kills bioluminescent T. cruziparasites in mice.•This JR1531 action in mice is boosted when combined with low doses of benznidazole.

Details

Language :
English
ISSN :
22137165
Volume :
28
Issue :
1
Database :
Supplemental Index
Journal :
Journal of Global Antimicrobial Resistance
Publication Type :
Periodical
Accession number :
ejs58516793
Full Text :
https://doi.org/10.1016/j.jgar.2021.10.030