The activity of fexinidazole (HOE 239) against experimental infections with <i>Trypanosoma cruzi</i>, trichomonads and <i>Entamoeba histolytica</i>

Raether, W.; Seidenath, H.

doi:10.1080/00034983.1983.11811668

Cited by 57 publications

(38 citation statements)

References 5 publications

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“…Among the hit compounds was the 5-nitroimidazole fexinidazole (Figure 1), first described in 1978 [46]. In its first incarnation, fexinidazole demonstrated potent in vitro and in vivo activity against trichomonads, Entamoeba histolytica , T. cruzi , and T. brucei [47]. When coadministered with suramin, fexinidazole was found to effectively cure the stage 2 mouse model of HAT.…”

Section: Nitro Drugs and The Trypanosomatids: Drug Rediscoverymentioning

confidence: 99%

Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects

Patterson

Wyllie

2014

Trends in Parasitology

272

217

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Section: Nitro Drugs and The Trypanosomatids: Drug Rediscoverymentioning

confidence: 99%

Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects

Patterson

Wyllie

2014

Trends in Parasitology

272

217

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“…Fexinidazole was described previously as having superior efficacy, compared with the current standard of care, i.e., benznidazole or nifurtimox, in an acute murine infection model of Chagas disease using the T. cruzi Brazil 32 strain (3). More recently, studies have confirmed that fexinidazole is effective in curing experimental T. cruzi infections in models of both acute and chronic stages of the disease, including infections with benznidazole-resistant T. cruzi strains (7).…”

mentioning

confidence: 79%

“…Nitroimidazoles are a well-known class of pharmacologically active compounds, several of which have shown good activity against trypanosomes (2). In the early 1980s, the nitroimidazole fexinidazole was shown to have activity against Trypanosoma cruzi, trichomonads, and Entamoeba histolytica (3). More recently, the molecule was "rediscovered" and selected for development by the Drugs for Neglected Diseases initiative (DNDi) in the exploration of new and old nitroimidazoles as drug leads for human African trypanosomiasis and Chagas disease.…”

mentioning

confidence: 99%

Antitrypanosomal Activity of Fexinidazole Metabolites, Potential New Drug Candidates for Chagas Disease

Bahia

Nascimento

Mazzeti

et al. 2014

Antimicrob Agents Chemother

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cThis study was designed to verify the in vivo efficacy of sulfoxide and sulfone fexinidazole metabolites following oral administration in a murine model of Chagas disease. Female Swiss mice infected with the Y strain of Trypanosoma cruzi were treated orally once per day with each metabolite at doses of 10 to 100 mg/kg of body weight for a period of 20 days. Parasitemia was monitored throughout, and cures were detected by parasitological and PCR assays. The results were compared with those achieved with benznidazole treatment at the same doses. Fexinidazole metabolites were effective in reducing the numbers of circulating parasites and protecting mice against death, compared with untreated mice, but without providing cures at daily doses of 10 and 25 mg/kg. Both metabolites were effective in curing mice at 50 mg/kg/day (30% to 40%) and 100 mg/kg/day (100%). In the benznidazole-treated group, parasitological cure was detected only in animals treated with the higher dose of 100 mg/kg/day (80%). Single-dose pharmacokinetic parameters for each metabolite were obtained from a parallel group of uninfected mice and were used to estimate the profiles following repeated doses. Pharmacokinetic data suggested that biological efficacy most likely resides with the sulfone metabolite (or subsequent reactive metabolites formed following reduction of the nitro group) following administration of either the sulfoxide or the sulfone and that prolonged plasma exposure over the 24-h dosing window is required to achieve high cure rates. Fexinidazole metabolites were effective in treating T. cruzi in a mouse model of acute infection, with cure rates superior to those achieved with either fexinidazole itself or benznidazole.

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“…2) whose trypanocidal activity was first discovered in the 1980s [25]. Fexinidazole was subsequently shown to be efficacious, with oral dosing, in the mouse model of stage 2 HAT (http://www.dndi.org/ portfolio/fexinidazole.html) and it was shown that the drug is metabolized to trypanocidal sulphoxide and sulphone metabolites (http://www.dndi.org/portfolio/ fexinidazole.html) [26] previously recognized in earlier studies [27]. In 2009, fexinidazole entered the phase I clinical trials which are presently ongoing.…”

Section: New Nitroheterocyclesmentioning

confidence: 96%

Potential new drugs for human African trypanosomiasis: some progress at last

Barrett

2010

Current Opinion in Infectious Diseases

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The activity of fexinidazole (HOE 239) against experimental infections with Trypanosoma cruzi, trichomonads and Entamoeba histolytica

Cited by 57 publications

References 5 publications

Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects

Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects

Antitrypanosomal Activity of Fexinidazole Metabolites, Potential New Drug Candidates for Chagas Disease

Potential new drugs for human African trypanosomiasis: some progress at last

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