title: Biological and chemical study of fused tri- and tetracyclic indazoles and analogues with important antiparasitic activity.
abstract: A series of fused tri- and tetracyclic indazoles and analogues compounds (NID) with potential antiparasitic effects were studied using voltamperometric and spectroscopic techniques. Nitroanion radicals generated by cyclic voltammetry were characterized by electron spin resonance spectroscopy (ESR) and their spectral lines were explained and analyzed using simulated spectra. In addition, we examined the interaction between radical species generated from nitroindazole derivatives and glutathione (GSH). Biological assays such as activity against Trypanosoma cruzi and cytotoxicity against macrophages were carried out. Finally, spin trapping and molecular modeling studies were also done in order to elucidate the potentials action mechanisms involved in the trypanocidal activity.
authors.affiliation: Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1, Chile.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Díaz-Urrutia
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Olea-Azar
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Zapata
authors.forename: Michel
authors.initials: M
authors.lastname: Lapier
authors.forename: Francisco
authors.initials: F
authors.lastname: Mura
authors.forename: Benjamín
authors.initials: B
authors.lastname: Aguilera-Venegas
authors.forename: Vicente J
authors.initials: VJ
authors.lastname: Arán
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: López-Múñoz
authors.forename: Juan D
authors.initials: JD
authors.lastname: Maya
mesh_terms: D000818:Animals; D000838:Anions; D000977:Antiparasitic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001681:Biological Assay; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003198:Computer Simulation; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D055664:Electrochemical Techniques; D004566:Electrodes; D004578:Electron Spin Resonance Spectroscopy; D007191:Indazoles / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008958:Models, Molecular; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry; D013113:Spin Labels; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000838:Anions; D000977:Antiparasitic Agents; D007191:Indazoles; D013113:Spin Labels; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D004121:Dimethyl Sulfoxide