Dinuclear doubly bridged phenoxido copper(II) complexes as efficient anticancer agents

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Materials Science

Background:

• Copper complexes are explored for their potential therapeutic applications.
• Developing novel metal-based anticancer agents is a significant area of research.

Purpose of the Study:

• To synthesize and characterize novel copper(II) complexes with diverse structures.
• To evaluate the in vitro antiproliferative activity of these complexes against human cancer cell lines.
• To investigate the mechanism of action of the most promising copper(II) complexes.

Main Methods:

• Synthesis and characterization of six copper(II) complexes using spectroscopic methods and X-ray crystallography.
• In vitro antiproliferative screening against multiple human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, MCF-7, HOS, A549, PANC-1, CaCo2, HeLa).
• Cell cycle analysis, cell uptake studies, and investigation of cell death pathways (apoptosis, autophagy, cuproptosis).

Main Results:

• Six copper(II) complexes with varying structures were successfully synthesized and characterized.
• Complexes 1-6 exhibited significant in vitro antiproliferative activity, with complex 6 showing superior efficacy compared to cisplatin.
• Complex 6 demonstrated broad-spectrum cytotoxicity across all tested cancer cell lines.
• Cell uptake studies indicated copper-independent cytotoxicity for complex 6.
• Complexes 4, 6, and 7 displayed distinct mechanisms of action, including apoptosis induction (complex 7) and autophagy induction (complexes 4 and 6), with potential cuproptosis induction by complexes 4 and 6.

Conclusions:

• Novel copper(II) complexes possess significant anticancer potential.
• Complex 6 is a promising lead compound for further anticancer drug development.
• The diverse mechanisms of action, including apoptosis, autophagy, and cuproptosis, highlight the versatility of these copper(II) complexes in cancer therapy.