title: Trypanosoma cruzi: in vitro activity of Epoxy-alpha-Lap, a derivative of alpha-lapachone, on trypomastigote and amastigote forms.
abstract: Chagas disease is an endemic parasitic infection caused by Trypanosomacruzi that affects 18-20 million people in Central and South America. Recently we described the Epoxy-alpha-Lap, an oxyran derivative of alpha-lapachone, which presents a low toxicity profile and a high inhibitory activity against T.cruzi epimastigotes forms, the non-infective form of this parasite. In this work we described the trypanocidal effects of Epoxy-alpha-Lap on extracellular (trypomastigote) and intracellular (amastigote) infective forms of two T. cruzi strains (Y and Colombian) known by their different infective profile. Our results showed that Epoxy-alpha-Lap is lethal to trypomastigote Y and Colombian strains (97% and 84%, respectively). Interestingly, Epoxy-alpha-Lap also showed a trypanocidal effect in human macrophage infected with T. cruzi Y (85.6%) and Colombian (71.9%) strains amastigote forms. Similar effects were observed on T. cruzi amastigote infected Vero cells (96.4% and 95.0%, respectively). Our results pointed Epoxy-alpha-Lap as a potential candidate for Chagas disease chemotherapy since it presents trypanocidal activity on all T. cruzi forms with low) toxicity profile.
authors.affiliation: Universidade Federal Fluminense, Departamento de Biologia Geral e Celular, Outeiro de São João Baptista, CEP 24020-150, Niterói, RJ, Brazil. saulocb@globo.com
authors.forename: S C
authors.initials: SC
authors.lastname: Bourguignon
authors.forename: H C
authors.initials: HC
authors.lastname: Castro
authors.forename: D O
authors.initials: DO
authors.lastname: Santos
authors.forename: C R
authors.initials: CR
authors.lastname: Alves
authors.forename: V F
authors.initials: VF
authors.lastname: Ferreira
authors.forename: I L
authors.initials: IL
authors.lastname: Gama
authors.forename: F C
authors.initials: FC
authors.lastname: Silva
authors.forename: W S
authors.initials: WS
authors.lastname: Seguins
authors.forename: R T
authors.initials: RT
authors.lastname: Pinho
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology*; D005347:Fibroblasts / Q000469:parasitology; D006801:Humans; D008018:Life Cycle Stages / Q000187:drug effects*; D008264:Macrophages / Q000469:parasitology; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development*; D014709:Vero Cells
chemical_list: C540757:2,2-dimethyl-3,4-dihydrospiro(benzo(g)chromene-10,2'-oxiran)-5(2H)-one; D004852:Epoxy Compounds; D009285:Naphthoquinones; D014344:Trypanocidal Agents; C415043:alpha-lapachone