title: New Imidazole-Based Compounds Active Against Trypanosoma cruzi.
abstract: 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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medicinal Biochemistry and Toxicology Laboratory, Department of Biological Sciences, PMB 1004, Landmark University, Omu-Aran. Nigeria.
authors.forename: Oluyomi Stephen
authors.initials: OS
authors.lastname: Adeyemi
authors.affiliation: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006, Madrid. Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Molina
authors.affiliation: Department of Chemical Sciences, Redeemer`s University, Ede. Nigeria.
authors.forename: Abiodun Omokehinde
authors.initials: AO
authors.lastname: Eseola
authors.affiliation: CEI Campus Moncloa, UCM-UPM & CSIC, Madrid. Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fonseca-Berzal
authors.affiliation: Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, Pza. Ramón y Cajal s/n, 28040 Madrid. Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Gómez-Barrio
mesh_terms: D000818:Animals; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy*; D018360:Crystallography, X-Ray; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D009593:Nitroimidazoles / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
chemical_list: D007093:Imidazoles; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C009999:benzonidazole
keywords: Azoles; Chagas disease; anti-parasitic agents; drug toxicity; trypanosomiasis