New Imidazole-Based Compounds Active Against Trypanosoma cruzi.

BACKGROUND

Current drugs available for the treatment of Chagas disease are fraught with several challenges including severe toxicity and limited efficacy. These factors coupled with the absence of effective drugs for treating the chronic stage of the disease have rendered the development of new drugs against Chagas disease a priority.

OBJECTIVE

This study screened several imidazole-based compounds for anti-Trypanosoma potential.

METHOD

Using an in vitro experimental infection model, several imidazole-based compounds were screened for anti-proliferative effect on Trypanosoma cruzi epimastigotes. Additionally, all test compounds were evaluated for unspecific cytotoxicity on L929 murine fibroblasts. Benznidazole (BZN) served as reference drug.

RESULTS

All test compounds demonstrated interesting trypanocidal potential with IC50 values in the μM range (1< 1C50 <8 μM). The activities of the test compounds compared favorably with BZN, which had an IC50 value ca. 30 μM. Conversely, most of the test compounds were highly cytotoxic, resulting in selectivity lower than that of BZN (SI > 9.42).

CONCLUSION

We provide evidence which implicate the imidazole-based compounds as potential prototypes for the development of anti-parasitic agents. Findings have far-reaching relevance to drug discovery efforts for trypanosomiasis.