Cytotoxic and ROS generation activity of anthraquinones chelate complexes with metal ions

Anthraquinones (AQs) are very effective chemotherapeutic agent, however their fundamental shortcoming is high cardiotoxicity caused by reactive oxygen species (ROS). Therefore, development of improved antitumor drugs with enhanced efficacy but reduced side effects remains a high priority. In the present study we evaluated the cytotoxicity and ROS generation activity of chelate complex of redox-active anthraquinone 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12-dione (Q1) with iron and copper ions. Cytotoxicity study was performed using the lung cancer cell line A549 and breast cancer cell line MDA-MB-231. Q1 and Cu-Q1 complex demonstrate high activity in these experiments, but Fe-Q1 complex inactive. The ROS generation activity has been studied by EPR spin trapping technique using A549, MDA-MB-231 cell lines, and T lymphoblast cell line MOLT-4. It was shown that Q1 is able to penetrate into these cells and participate in redox reactions with the formation of a semiquinone radical. Fe(III) chelate complex formation results in much slower kinetics of ROS generation compared with pure Q1, which could be connected with a lower penetration through the cell membrane.