Comparative studies of nifurtimox uptake and metabolism by drug-resistant and susceptible strains of Trypanosoma cruzi

Tsuhako, Maria Heloisa; Alves, Maria Júlia M.; Colli, Walter; Filardi, Leny S.; Brener, Z.; Augusto, Ohára

doi:10.1016/0742-8413(91)90248-r

Cited by 12 publications

(11 citation statements)

References 15 publications

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“…These drugs cure only a very low percentage of chronic patients (Rodrigues-Coura & de Castro 2002). Natural resistance of T. cruzi to nitro derivatives was suggested as an important factor to explain the low rates of cure detected in chagasic patients (Tsuhako et al 1991).…”

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confidence: 99%

Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes

Chena¹,

Elizondo-Jiménez²,

Rodrı́guez-Páez³

et al. 2004

Mem. Inst. Oswaldo Cruz

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confidence: 99%

Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes

Chena¹,

Elizondo-Jiménez²,

Rodrı́guez-Páez³

et al. 2004

Mem. Inst. Oswaldo Cruz

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“…Nifurtimox is able to virtually destroy parasites and yet not produce morphological changes in the non-infected tissue cells at this concentration (Voigt et al 1972). However, studies regarding the mode of action of nifurtimox employ higher concentrations (de Castro and Meirelles 1990;Tsuhako et al 1991). Quantitative determination of nifurtimox in human body¯uids showed that, after a dose of 5 mg/kg orally 3 times daily for 3 days, serum concentration of Lampit varied from 0.7 to 1 lg/ml during the ®rst 50 h (Mendenwald et al 1972).…”

Section: Discussionmentioning

confidence: 99%

In vitro effects of anti- Trypanosoma cruzi compounds on HSP60 levels

Muelas-Serrano

Pérez-Serrano

Gómez‐Barrio

et al. 2001

Parasitology Research

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The effect of nifurtimox and 5-nitro-2-thienylmalononitrile (5NO2TM), a novel compound with anti-Trypanosoma cruzi activity, upon vitality and HSP60 immunoreactivity of epimastigotes, has been determined. Both products showed no activity against epimastigotes at 0.1 microg/ml, while at 0.5 and 1 microg/ml, after 24 h of incubation, densities of these groups were significantly reduced, when compared to controls. An enhancement of HSP60 immunoreactivity was observed after 24 h in groups treated with 0.5 and 1 microg/ml nifurtimox. On the other hand, 5NO2TM had no effect.

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“…The T. cruzi Y strain used in this study was previously characterized to be partially resistant to benznidazole (27) and most likely to other nitrocompounds that are activated by NTRs. In addition, it has been suggested that drug uptake played a more important role than drug metabolism in modulating resistance to nifurtimox in T. cruzi strains (28). This may be the case for compound 4 as well, since it is less lipophilic than compounds 3 and 5 (it had a lower value of the calculated logarithm of the partition coefficient between n-octanol and water [clogP]) (13).…”

Section: Discussionmentioning

confidence: 99%

Nitrotriazole-Based Compounds as Antichagasic Agents in a Long-Treatment In Vivo Assay

Papadopoulou

Bloomer

Rosenzweig

et al. 2017

Antimicrob Agents Chemother

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3-Nitrotriazole-based compounds belonging to various chemical subclasses were found to be very effective against Chagas disease both in vitro and in vivo after a short administration schedule. In this study, five compounds with specific characteristics were selected to be administered for longer periods of time to mice infected with the virulent Trypanosoma cruzi Y strain to further evaluate their effectiveness as antichagasic agents and whether or not potential adverse effects occur. Benznidazole was included for comparison purposes. Complete parasitemia depletion, weight gain, 100% survival, and a lack of myocardial inflammation were observed with four of the compounds and benznidazole administered intraperitoneally at 15 or 20 mg/kg of body weight/day for 40 days. There was a significant reduction in the number of treatment days (number of doses) necessary to induce parasitemia suppression with all four compounds compared to that required with benznidazole. Partial cures were obtained with only one compound tested at 15 mg/kg/day and on the schedule mentioned above but not with benznidazole. Taken together, our data suggest that these compounds demonstrate potent trypanocidal activity comparable to or better than that of the reference drug, benznidazole, when they are administered at the same dose and on the same schedule.

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Comparative studies of nifurtimox uptake and metabolism by drug-resistant and susceptible strains of Trypanosoma cruzi

Cited by 12 publications

References 15 publications

Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes

Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes

In vitro effects of anti- Trypanosoma cruzi compounds on HSP60 levels

Nitrotriazole-Based Compounds as Antichagasic Agents in a Long-Treatment In Vivo Assay

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