title: 2-Phenylaminonaphthoquinones and related compounds: synthesis, trypanocidal and cytotoxic activities.
abstract: A series of new 2-aminonaphthoquinones and related compounds were synthesized and evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity and selectivity as compared with current trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than nifurtimox against Trypanosoma cruzi in comparison with Vero cells. Some of the synthesized quinones were tested against cancer cells and normal fibroblasts, showing that certain chemical modifications on the naphthoquinone moiety induce and excellent increase the selectivity index of the cytotoxicity (4g and 10). The results presented here show that the anti-T. cruzi activity of 2-aminonaphthoquinones derivatives can be improved by the replacement of the benzene ring by a pyridine moiety. Interestingly, the presence of a chlorine atom at C-3 and a highly lipophilic alkyl group or aromatic ring are newly observed elements that should lead to the discovery of more selective cytotoxic and trypanocidal compounds.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile.
authors.forename: Ivan
authors.initials: I
authors.lastname: Sieveking
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Thomas
authors.affiliation: Centro Singular de Investigación en Química Biológica y Materiales Moleculares and Departamento de Química Orgánica (Facultad de Química), Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Estévez
authors.affiliation: Facultad de Farmacia, Universidad de Valparaíso, Av. Gran Bretaña N 1093, Valparaíso, Chile.
authors.forename: Natalia
authors.initials: N
authors.lastname: Quiñones
authors.affiliation: Facultad de Farmacia, Universidad de Valparaíso, Av. Gran Bretaña N 1093, Valparaíso, Chile.
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Cuéllar
authors.affiliation: Centro de Investigaciones Biomédicas, Escuela de Medicina, Universidad de Valparaíso, Av. Hontaneda N° 2664, Valparaíso, Chile.
authors.forename: Juan
authors.initials: J
authors.lastname: Villena
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, 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, 702843 Santiago de Chile, Chile.
authors.forename: Angélica
authors.initials: A
authors.lastname: Fierro
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Tapia
authors.affiliation: Instituto de Ciencias Biomédicas, Programa de Farmacología Molecular y Clínica, Universidad de Chile, PO Box 70000, Santiago, Chile.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Maya
authors.affiliation: Instituto de Ciencias Biomédicas, Programa de Farmacología Molecular y Clínica, Universidad de Chile, PO Box 70000, Santiago, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: López-Muñoz
authors.affiliation: Departamento de Química, Facultad de Ciencias, Universidad de Chile, PO Box 653, Santiago, Chile.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Cassels
authors.affiliation: Centro Singular de Investigación en Química Biológica y Materiales Moleculares and Departamento de Química Orgánica (Facultad de Química), Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: ramon.estevez@usc.es.
authors.forename: Ramon J
authors.initials: RJ
authors.lastname: Estévez
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile. Electronic address: cosalas@uc.cl.
authors.forename: Cristian O
authors.initials: CO
authors.lastname: Salas
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D000814:Aniline Compounds; D009285:Naphthoquinones; D014344:Trypanocidal Agents
keywords: 2-Phenylaminonaphthoquinones; Benzocarbazolequinones; Cytotoxicity; Electronic properties; T. cruzi