title: Trypanosoma cruzi: activities of lapachol and alpha- and beta-lapachone derivatives against epimastigote and trypomastigote forms.
abstract: Derivatives of natural quinones with biological activities, such as lapachol, alpha- and beta-lapachones, have been synthesized and their trypanocidal activity evaluated in vitro in Trypanosoma cruzi cells. All tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity as compared with current trypanocidal drugs, nifurtimox and benznidazole. The results presented here show that the anti-T. cruzi activity of the alpha-lapachone derivatives can be increased by the replacement of the benzene ring by a pyridine moiety. Free radical production and consequently oxidative stress through redox cycling or production of electrophilic metabolites are the potential biological mechanism of action for these synthetic quinones.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Macul, Santiago 6094411, Chile. cosalas@uc.cl
authors.forename: Cristian
authors.initials: C
authors.lastname: Salas
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Tapia
authors.forename: Karina
authors.initials: K
authors.lastname: Ciudad
authors.forename: Verónica
authors.initials: V
authors.lastname: Armstrong
authors.forename: Myriam
authors.initials: M
authors.lastname: Orellana
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kemmerling
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferreira
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
authors.forename: Antonio
authors.initials: A
authors.lastname: Morello
mesh_terms: D000818:Animals; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D009285:Naphthoquinones; D014344:Trypanocidal Agents; C014638:beta-lapachone; C008252:lapachol; C415043:alpha-lapachone