ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Copper complexes with N and O-donor ligands in cancer treatment: unlocking therapeutic power through chelation and emerging trends (2020–2025)

Alaa Shafie, Amal Adnan Ashour, Faris J. Tayeb, and Mohammed Fareed Felemban

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia

E-mail: a.shafie@tu.edu.sa

Abstract:

The ongoing battle against cancer has driven the development of novel therapeutic strategies, with copper-based complexes containing N- and O- donor ligands gaining increasing attention. These compounds stand out due to their inherent redox properties, ability to generate reactive oxygen species (ROS), and selective toxicity toward cancer cells. Furthermore, their structural similarity to endogenous metalloenzymes allows them to interfere with vital cellular pathways, positioning them as promising anticancer agents. Chelation plays a pivotal role in amplifying the biological performance of these copper complexes. By stabilizing the metal center, chelation enhances solubility, membrane permeability, and targeted delivery. It also strengthens DNA-binding affinity through intercalation, groove binding, or backbone interaction, promoting DNA damage and apoptosis in tumor cells while sparing healthy tissues. These chelated systems exhibit improved pharmacokinetics and reduced systemic toxicity, offering a significant therapeutic edge over conventional treatments. This review explores significant advances from 2020 to 2025 in the design and application of copper complexes with N- and O-donor ligands for cancer therapy and diagnosis. The discussion emphasizes complexation behavior, mechanistic insights, and recent advances in therapeutic efficacy. We hope this review will inspire and support researchers in developing next-generation copper-based anticancer agents.

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-04948-6

Chemical Papers 80 (10) 11363–11382 (2026)