title: Synthesis, half-wave potentials and antiproliferative activity of 1-aryl-substituted aminoisoquinolinequinones.
abstract: The synthesis of a variety of 1-aryl-7-phenylaminoisoquinolinequinones from 1,4-benzoquinone and arylaldehydes via the respective 1-arylisoquinolinequinones is reported. The cyclic voltammograms of the new compounds exhibit two one-electron reduction waves to the corresponding radical-anion and dianion and two quasi-reversible oxidation peaks. The half-wave potential values (EI½) of the members of the series have proven sensitive to the electron-donor effect of the aryl group (phenyl, 2-thienyl, 2-furyl) at the 1-position as well as to the phenylamino groups (anilino, p-anisidino) at the 7-position. The antiproliferative activity of the new compounds was evaluated in vitro using the MTT colorimetric method against one normal cell line (MRC-5 lung fibroblasts) and two human cancer cell lines: AGS human gastric adenocarcinoma and HL-60 human promyelocytic leukemia cells in 72-h drug exposure assays. Among the series, compounds 5a, 5b, 5g, 5h, 6a and 6d exhibited interesting antiproliferative activities against human gastric adenocarcinoma. The 1-arylisoquinolinequinone 6a was found to be the most promising active compound against the tested cancer cell lines in terms of IC50 values (1.19; 1.24 µM) and selectivity index (IS: 3.08; 2.96), respect to the anti-cancer agent etoposide used as reference (IS: 0.57; 0.14).
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile. juana.ibacache.r@usach.cl.
authors.forename: Juana Andrea
authors.initials: JA
authors.lastname: Ibacache
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile.
authors.forename: Virginia
authors.initials: V
authors.lastname: Delgado
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile.
authors.forename: Julio
authors.initials: J
authors.lastname: Benites
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile.
authors.forename: Cristina
authors.initials: C
authors.lastname: Theoduloz
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile.
authors.forename: Verónica
authors.initials: V
authors.lastname: Arancibia
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile.
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile. jvalderr@uc.cl.
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Valderrama
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000737:chemistry*; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D011809:Quinones