Synthesis, antiproliferative activity and mechanism of copper(II)-thiosemicarbazone complexes as potential anticancer and antimicrobial agents

Abstract

Malignant tumors have become one of the challenges to global human health today, and the development of new drugs has become a research hotspot for tumor treatment. In order to prove that copper(II)-thiosemicarbazone complexes can be used as antibacterial and antitumor agents, we have synthesized and characterized three copper(II) complexes (C1-C3). These Cu(II) complexes exhibited excellent anticancer and antimicrobial activity, and greatly exceed the corresponding metal-free ligands. C3 has the highest anti-proliferative activity (0.20 ± 0.04 µM) against A549 (human lung carcinoma cell lines) and the best inhibitory zone diameter (25.78 ± 0.18 mm) against E. coli. The lipophilicity of the ligand is closely related to the anti-proliferative and antibacterial activities of these Cu(II) complexes. The study of the cellular mechanism demonstrates that these Cu(II) complexes promoted cell apoptosis by catalyzing hydrogen peroxide to produce intracellular reactive oxygen species (ROS). Antibacterial experiments showed that these Cu(II) complexes exhibited potent antibacterial activities, especially against gram-negative bacteria. These Cu(II) complexes may initially cause outer membrane/lipopolysaccharide (LPS) instability, disrupt cell membranes, and ultimately lead to bacterial cell lysis.

Graphical Abstract

Keywords:

• Copper complex
• thiosemicarbazone
• anticancer activity
• antimicrobial activity
• apoptosis

Disclosure statement

The authors declare that they have no conflict of interests.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (81571812), Pingdingshan College PhD Startup Fund under Grant PXY-BSQD-202003; key specialized research and development breakthrough in Henan province (202102310476 and 182102310181); and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions under Grant 1107047002.