Synthesis, Half-Wave Potentials and Antiproliferative Activity of 1-Aryl-substituted Aminoisoquinolinequinones

Molecules

Juana Andrea Ibacache³  Virginia Delgado³  Julio Benites⁴  Cristina Theoduloz²  Verónica Arancibia³  Giulio G. Muccioli¹ 

[1] Bioanalysis and Pharmacology of Bioactive Lipids Laboratory, Louvain Drug Research Institute, Université Catholique de Louvain, 72 Avenue E. Mounier, BPBL 7201, Brussels 1200, Belgium;Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile;Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile;Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile

关键词: isoquinolinequinones;    enaminones;    half-wave potential;    antiproliferative activity;    SAR analysis;   

DOI  :  10.3390/molecules19010726

来源: mdpi

【 摘 要 】

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 (E^I_½) 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).

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.