Oluyomi Stephen Adeyemi, María Teresa Molina , Abiodun Omokehinde Eseola , Cristina Fonseca-Berzal and Alicia Gómez-Barrio Pages 20 - 24 ( 5 )
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.
Azoles, anti-parasitic agents, drug toxicity, trypanosomiasis, Chagas disease.
Medicinal Biochemistry and Toxicology Laboratory, Department of Biological Sciences, PMB 1004, Landmark University, Omu-Aran, Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006, Madrid, Department of Chemical Sciences, Redeemer`s University, Ede, CEI Campus Moncloa, UCM-UPM & CSIC, Madrid, Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, Pza. Ramón y Cajal s/n, 28040 Madrid