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Novel 3-nitro-1H-1,2,4-triazole-based compounds as potential anti-Chagasic drugs : in vivo studies

Papadopoulou, Maria V. and Bloomer, William D. and Rosenzweig, Howard S. and Ashworth, Rachel and Wilkinson, Shane R. and Kaiser, Marcel and Andriani, Grasiella and Rodriguez, Ana. (2013) Novel 3-nitro-1H-1,2,4-triazole-based compounds as potential anti-Chagasic drugs : in vivo studies. Future medicinal chemistry, Vol. 5, H. 15. pp. 1763-1776.

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Official URL: http://edoc.unibas.ch/dok/A6194649

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Abstract

Background: Chagas disease is caused by the parasite Trypanosoma cruzi, is endemic in Latin America and leads to an estimated 14,000 deaths per year and around 100 million people at risk of infection. Drugs currently used in the treatment of Chagas are old, partially effective and have numerous side effects. Methodology: We have previously reported that 3-nitro-1H-1,2,4-triazole-based compounds demonstrate significant and selective activity against T. cruzi amastigotes in infected L6 cells via activation of a type I nitroreductase, specific to trypanosomatids. In the present work we evaluated in vivo 13 of these compounds based on their high in vitro potency against T. cruzi (IC50 > 1 µM) and selectivity (SI: toxicity to L6 cells/toxicity against T. cruzi amastigotes < 200). Representative compounds of different chemical classes were included. A fast luminescence assay with transgenic parasites that express luciferase, and live imaging techniques were used. A total of 11 out of 13 compounds demonstrated significant antichagasic activity when administered intraperitoneally for 5-10 days at relatively small doses. The best in vivo activity was demonstrated by amides and sulfonamide derivatives. ADMET studies were performed for specific compounds. Conclusion: At least three compounds were identified as effective, non-toxic antichagasic agents suitable for further development.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Kaiser, Marcel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Future Science
ISSN:1756-8919
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Mar 2014 13:12
Deposited On:27 Mar 2014 13:12

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