Synthesis and <em>in Vitro</em> Cytotoxic Evaluation of Aminoquinones Structurally Related to Marine Isoquinolinequinones

Abstract

The synthesis of 4-methoxycarbonyl-3-methylisoquinolinequinone (<strong>1</strong>) and a variety of its substitution products with amino-, alkylamino and halogen groups on the quinone nucleus is reported. The series of 6-, 7- and 6,7-subtituted isoquinolinequinones were evaluated <em>in vitro</em> for their cytotoxic activity using the MTT colorimetric method. All the newly synthesized compounds showed moderate to high potency against MRC-5 healthy lung fibroblasts and four human tumor cell lines: AGS gastric adenocarcinoma, SK-MES-1 lung, J82 bladder carcinoma, and HL-60 leukemia cells. Among the series, compounds <strong>4b</strong>, <strong>12</strong> and <strong>13</strong> exhibited interesting antitumor activity against human gastric adenocarcinoma, human lung and human bladder carcinoma cancer cells. 7-Amino-6-bromoisoquinoline-5,8-quinone (<strong>13</strong>) was found to be the most promising active compound against the tested cancer cell lines, with IC₅₀ values in the 0.21−0.49 mM range, lower than the anti-cancer agent etoposide used as reference.

Keywords

• aminoisoquinoline-5,8-quinones
• regioselectivity
• anticancer
• SAR analysis