title: Synthesis and biological characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal agents.
abstract: A new indole-4,9-dione and their phenoxy derivatives were synthesized and evaluated in vitro against the epimastigote form of Trypanosoma cruzi, Y strain. All of these novel compounds were found to be extremely potent and selective that the standard drug nifurtimox. Interestingly, phenoxyindole-4,9-dione 9d displayed excellent nanomolar inhibitory activity, IC50=20 nM, and high selectivity index, SI=625. In silico studies using MOE program were performed to generate a preliminary pharmacophore model.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile. Electronic address: rtapia@uc.cl.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Tapia
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile.
authors.forename: Cristian O
authors.initials: CO
authors.lastname: Salas
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile.
authors.forename: Karina
authors.initials: K
authors.lastname: Vázquez
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile.
authors.forename: Christian
authors.initials: C
authors.lastname: Espinosa-Bustos
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Soto-Delgado
authors.affiliation: Grupo de Química Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, Uruguay.
authors.forename: Javier
authors.initials: J
authors.lastname: Varela
authors.affiliation: Grupo de Química Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, Uruguay.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Birriel
authors.affiliation: Grupo de Química Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, Uruguay; Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo, Uruguay.
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.affiliation: Grupo de Química Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, Uruguay.
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.affiliation: Centro de Bioinformática Estructural-DETEMA, Facultad de Química, Universidad de la República, C.C. 1157, Montevideo, Uruguay.
authors.forename: Margot
authors.initials: M
authors.lastname: Paulino
mesh_terms: D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D007211:Indoles; D014344:Trypanocidal Agents
keywords: Anti-T. cruzi; Cytotoxicity; Indolequinones; Pharmacophore model