title: In vitro activity of N-benzenesulfonylbenzotriazole on Trypanosoma cruzi epimastigote and trypomastigote forms.
abstract: Chagas disease is still an important health problem in Central and South America. However, the only drugs currently available for specific treatment of this disease may induce toxic side effects in the host. The aim of this work was to determine the activity of N-benzenesulfonylbenzotriazole (BSBZT) against the protozoan parasite Trypanosoma cruzi. The effects of BSBZT and benzotriazole (BZT) were compared to those of benznidazole (BZL) on epimastigote and trypomastigote forms. BSBZT was found to have an in vitro growth inhibitory dose-dependent activity against epimastigotes, with flow cytometry analysis confirming that the treated parasites presented size reduction. BSBZT showed an IC(50) of 21.56 μg/mL (81.07 μM) against epimastigotes at 72 h of incubation, whereas BZT did not affect the growth of this parasite form. Furthermore, the toxic effect of BSBZT, was stronger and appeared earlier (at 24h) in trypomastigotes than in epimastigotes, with the LC(50) of this compound being 28.40 μg/mL (106.79 μM) against trypomastigotes. The concentrations of BSBZT used in this study presented low hemolytic activity and cytotoxicity. Consequently, at concentrations near IC(50) and LC(50) (25μg/mL), BSBZT caused only 2.4% hemolysis and 15% of RAW 264.7 cell cytotoxicity. These results reveal the potential of BSBZT as a prototype in drug design for developing new anti-T. cruzi compounds.
authors.affiliation: Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Instituto Multidisciplinario de Biología Vegetal, IMBIV-CONICET, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Córdoba, Argentina. becerra@fcq.unc.edu.ar
authors.forename: M C
authors.initials: MC
authors.lastname: Becerra
authors.forename: N
authors.initials: N
authors.lastname: Guiñazú
authors.forename: L Y
authors.initials: LY
authors.lastname: Hergert
authors.forename: A
authors.initials: A
authors.lastname: Pellegrini
authors.forename: M R
authors.initials: MR
authors.lastname: Mazzieri
authors.forename: S
authors.initials: S
authors.lastname: Gea
authors.forename: I
authors.initials: I
authors.lastname: Albesa
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D014355:Chagas Disease / Q000469:parasitology; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009593:Nitroimidazoles / Q000494:pharmacology* / Q000633:toxicity; D013449:Sulfonamides / Q000494:pharmacology* / Q000633:toxicity; D014230:Triazoles / Q000494:pharmacology* / Q000633:toxicity; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
chemical_list: D009593:Nitroimidazoles; D013449:Sulfonamides; D014230:Triazoles; D014344:Trypanocidal Agents; C009999:benzonidazole