Hydroxymethylnitrofurazone is active in a murine model of Chagas disease.

CAROLINA DAVIES,; RUBÉN MARINO CARDOZO; OLGA SÁNCHEZ NEGRETTE; MARÍA CELIA MORA; MAN CHIN CHUNG; MIGUEL ÁNGEL BASOMBRÍO.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

AMER SOC MICROBIOLOGY

Lugar: Washington, DC; Año: 2010 vol. 54

0066-4804

The addition of a hydroxymethyl group to the antimicrobial drug, nitrofurazone, generated hydroxymethylnitrofurazone (NFOH) which had reduced toxicity when tested against Trypanosoma cruzi in a murine model of Chagas’ disease. Four groups of 12 Swiss female mice received 150 mg/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole, or the solvent as placebo. Treatments were administered orally once a day, 6 days a week until completing 60 doses. NFOH was as effective as benznidazole (BZL) in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after finishing the treatments, a time when levels of anti-T. cruzi antibodies were very low in mice treated either with NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative NFOH displayed the lowest mortality (16%), followed by BZL (33%) and placebo (66%). Histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart, and NFOH the lowest. The present evidence suggests that NFOH is a promising anti-T. cruzi agent.