Image-based in vitro screening reveals the trypanostatic activity of hydroxymethylnitrofurazone against Trypanosoma cruzi

Made available in DSpace on 2022-04-29T08:45:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-07-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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-out assays and real-time microscopy. For animal experi-mentation, BALB/c mice were inoculated with the bioluminescent reporter strain and assessed by highly sensitive in vivo and ex vivo imaging. Cyclophosphamide treatment was used to promote parasite relapse in the chronic stage of infection. Our data show that NFOH acts by a trypanostatic mechanism, and that it is more active than BZN in vitro against the infectious trypomastigote form of Trypanosoma cruzi. We also found that it is more effective at curing experimental infections in the chronic stage, compared with the acute stage, a feature that it shares with BZN. Therefore, given its reduced toxicity, enhanced anti-trypomastigote activity, and curative properties, NFOH can be considered as a potential therapeutic option for Chagas disease, perhaps in combination with other trypanocidal agents. School of Pharmaceutical Sciences Sao Paulo State University (UNESP) Department of Infection Biology Faculty of Infectious and Tropical Diseases London School of Hygiene and Tropical Medicine, Keppel Street LAPEN—Laboratory of Design and Synthesis of Chemotherapeutic Agents Potentially Active on Neglected Diseases Department of Pharmacy School of Pharmaceutical Sciences University of Sao Paulo (USP) Advanced Research Center in Medicine School of Medicine Union of the Colleges of the Great Lakes (UNILAGO) School of Pharmaceutical Sciences Sao Paulo State University (UNESP) FAPESP: 2016/10847-9