title: New potent imidazoisoquinolinone derivatives as anti-Trypanosoma cruzi agents: biological evaluation and structure-activity relationships.
abstract: A series of novel benzoimidazo and N-aryl-5-oxo-imidazo[1,2-b]isoquinoline-10-carbothioamides was developed. All the compounds were evaluated for their in vitro action against the epimastigote form of Trypanosoma cruzi. Four of them showed higher activity than Nifurtimox. Their unspecific cytotoxicity was evaluated using HeLa and L6 cells, being non-toxic at concentrations at least 15 and 200 times higher than that of T. cruzi IC(50.) To gain insight into the mechanism of action, their DNA binding properties and reactivity with glutathione were studied, and QSAR study was performed.
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina.
authors.forename: Mariela
authors.initials: M
authors.lastname: Bollini
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Casal
authors.forename: Diego E
authors.initials: DE
authors.lastname: Alvarez
authors.forename: Lucía
authors.initials: L
authors.lastname: Boiani
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.forename: Ana María
authors.initials: AM
authors.lastname: Bruno
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy; D016054:DNA, Protozoan / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D007546:Isoquinolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D008958:Models, Molecular; D010084:Oxidation-Reduction / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D016054:DNA, Protozoan; D007093:Imidazoles; D007546:Isoquinolines; D014344:Trypanocidal Agents; D005978:Glutathione