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).
Keywords: isoquinolinequinones; enaminones; half-wave potential; antiproliferative activity; SAR analysis
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Ibacache, J.A.; Delgado, V.; Benites, J.; Theoduloz, C.; Arancibia, V.; Muccioli, G.G.; Valderrama, J.A. Synthesis, Half-Wave Potentials and Antiproliferative Activity of 1-Aryl-substituted Aminoisoquinolinequinones. Molecules 2014, 19, 726-739.
Ibacache JA, Delgado V, Benites J, Theoduloz C, Arancibia V, Muccioli GG, Valderrama JA. Synthesis, Half-Wave Potentials and Antiproliferative Activity of 1-Aryl-substituted Aminoisoquinolinequinones. Molecules. 2014; 19(1):726-739.
Ibacache, Juana A.; Delgado, Virginia; Benites, Julio; Theoduloz, Cristina; Arancibia, Verónica; Muccioli, Giulio G.; Valderrama, Jaime A. 2014. "Synthesis, Half-Wave Potentials and Antiproliferative Activity of 1-Aryl-substituted Aminoisoquinolinequinones." Molecules 19, no. 1: 726-739.