Rapid test for the evaluation of the activity of the prodrug hydroxymethylnitrofurazone in the processing of Trypanosoma cruzi messenger RNAs.
نویسندگان
چکیده
No fully effective treatment has been developed since the discovery of Chagas' disease by Carlos Chagas in 1909. Since drug-resistant Trypanosoma cruzi strains are occurring and the current therapy is effectiveness in the acute phase but with various adverse side effects, more studies are needed to characterize the susceptibility of T. cruzi to new drugs. Many natural and/or synthetic substances showing trypanocidal activity have been used, even though they are not likely to be turned into clinically approved drugs. Originally, drug screening was performed using natural products, with only limited knowledge of the molecular mechanism involved in the development of diseases. Trans-splicing, which is unusual RNA processing reaction and occurs in nematodes and trypanosomes, implies the processing of polycistronic transcription units into individual mRNAs; a short transcript spliced leader (SL RNA) is trans-spliced to the acceptor pre-mRNA, giving origin to the mature mRNA. In the present study, permeable cells of T. cruzi epimastigote forms (Y, BOL and NCS strains) were treated to evaluate the interference of two drugs (hydroxymethylnitrofurazone - NFOH-121 and nitrofurazone) in the trans-splicing reaction using silver-stained PAGE analysis. Both drugs induced a significant reduction in RNA processing at concentrations from 5 to 12.5 microM. These data agreed with the biological findings, since the number of parasites decreased, especially with NFOH-121. This proposed methodology allows a rapid and cost-effective screening strategy for detecting drug interference in the trans-splicing mechanism of T. cruzi.
منابع مشابه
Trypanocidal activity of some endemic species of Satureja in Iran
Trypanosoma cruzi, a hemoflagellate protozoan (family Trypanosomatidae), is the ethiological agent of Chagas disease, which is affecting 16-18 million people, with more than 100 million exposed to the risk of infection. Higher plants are a potential source of new drugs to improve the treatment of Chagase disease. Until recently, Rutacea, Meliaceae, Simaroubaceae and Burceraceae families have be...
متن کاملEffects of some fractions from Achillea biebersteinii and A.millefolium on the epimastigotes of Trypanosoma cruzi
Higher plants are a potential source of new drugs to improve the treatment of Chagase disease, which is affecting 16-18 million people, with more than 100 million exposed to the risk of infection (Ambrozin et al., 2004; Coura & Castro, 2002). Current therapy is unsatisfactory, because the only two drugs available, benznidazole and nifortimox possess severe side effects and their activity is lim...
متن کاملEffects of some fractions from Achillea biebersteinii and A.millefolium on the epimastigotes of Trypanosoma cruzi
Higher plants are a potential source of new drugs to improve the treatment of Chagase disease, which is affecting 16-18 million people, with more than 100 million exposed to the risk of infection (Ambrozin et al., 2004; Coura & Castro, 2002). Current therapy is unsatisfactory, because the only two drugs available, benznidazole and nifortimox possess severe side effects and their activity is lim...
متن کاملTrypanocidal activity of some endemic species of Satureja in Iran
Trypanosoma cruzi, a hemoflagellate protozoan (family Trypanosomatidae), is the ethiological agent of Chagas disease, which is affecting 16-18 million people, with more than 100 million exposed to the risk of infection. Higher plants are a potential source of new drugs to improve the treatment of Chagase disease. Until recently, Rutacea, Meliaceae, Simaroubaceae and Burceraceae families have be...
متن کاملTrypanocidal Activity of Some Medicinal Plants Against the Epimastigotes of Trypanosoma cruzi
Background: Some of medicinal plants are a potential source of new drugs to improve the treatment of Chagase disease whose treatment is still a challenge. Here in this screening, the in vitro trypanocidal activity of some fractions for 16 medicinal plants, collected from the northern part of Iran, has been reported. Methods: Aerial parts of the plants were dried carefully and followed by ex...
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ورودعنوان ژورنال:
- Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
دوره 40 1 شماره
صفحات -
تاریخ انتشار 2007