2021
DOI: 10.3390/ijms22136930
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Image-Based In Vitro Screening Reveals the Trypanostatic Activity of Hydroxymethylnitrofurazone against Trypanosoma cruzi

Abstract: Hydroxymethylnitrofurazone (NFOH) is a therapeutic candidate for Chagas disease (CD). It has negligible hepatotoxicity in a murine model compared to the front-line drug benznidazole (BZN). Here, using Trypanosoma cruzi strains that express bioluminescent and/or fluorescent reporter proteins, we further investigated the in vitro and in vivo activity of NFOH to define whether the compound is trypanocidal or trypanostatic. The in vitro activity was assessed by exploiting the fluorescent reporter strain using wash… Show more

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Cited by 7 publications
(7 citation statements)
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“…The NFOH nanocrystals described in the present study (NFOH-F1 and NFOH-F2) exhibited similar activities compared with free NFOH [14][15][16][17]. Likewise, considering the fact that the NFOH nanocrystals can be tested against other strains of T. cruzi or Leishmania in animal assays, the present results are important to future studies on NFOH (free, nanocrystals, or polymers).…”
Section: Discussionsupporting
confidence: 61%
See 1 more Smart Citation
“…The NFOH nanocrystals described in the present study (NFOH-F1 and NFOH-F2) exhibited similar activities compared with free NFOH [14][15][16][17]. Likewise, considering the fact that the NFOH nanocrystals can be tested against other strains of T. cruzi or Leishmania in animal assays, the present results are important to future studies on NFOH (free, nanocrystals, or polymers).…”
Section: Discussionsupporting
confidence: 61%
“…Hydroxymethylnitrofurazone (NFOH) is a nitrofurazone prodrug (Figure 1), which has been considered a crucial and promising anti-T. cruzi candidate in vitro [14,15]. Its activity was evaluated and confirmed in murine models with acute and chronic stages of Chagas disease [15][16][17].…”
Section: Introductionmentioning
confidence: 99%
“…Regarding BNZ, NFX, hydroxymethylnitrofurazone (NFOH) and fexinidazole, they are all described to be prodrugs, which upon being metabolized generate highly reactive intermediary compounds that can target many cellular components ( Maya et al., 2007 ; Hall et al., 2011 ; Scarim et al., 2021 ). In particular, these drugs would be mainly metabolized by T. cruzi nitroreductase (TcCLB.510611.60, UniProtKB Q4D8D9) ( Maya et al., 2007 ; Hall et al., 2011 ).…”
Section: Resultsmentioning
confidence: 99%
“…Also, NFOH (91) hepatotoxicity was assessed in in vitro experiments with HepG2 cells, and it caused an enhancement in ROS generation and in the oxidative damage to DNA biomarker 8-oxo-29-deoxyguanosine (8oxo-dG). Despite this, cell viability was not significantly (Davis et al, 2010;Ekins et al, 2015;Scarim et al, 2018;Scarim et al, 2021a changed by the administration of NFOH (91). On the other hand, the cells treated with BNZ showed no increase in this biomarker, but they exhibited a reduction in cell viability, displaying 33% cell death at 100 μM (Davies et al, 2014).…”
Section: Toxicity Evaluationmentioning
confidence: 99%