Delineating the Mechanisms of Action of Copper-based Therapeutics: A Comprehensive Narrative Review

Abstract

Copper-based therapeutics have emerged as a promising frontier in modern metallopharmaceutical research. Copper possesses properties of unique redox activity, coordination flexibility, and multifaceted biological functions. This review discusses the metabolic significance of essential metals in human physiology, with particular emphasis on copper and its therapeutic potential. Copper plays indispensable roles in mitochondrial respiration, antioxidant defence, neurotransmitter synthesis, connective tissue formation, and iron metabolism through various copper-dependent enzymes and transport systems. The dualistic nature of copper, being both essential and potentially cytotoxic, forms the mechanistic basis for its biomedical applications. Copper complexes, nanoparticles, ionophores, and chelators exhibit remarkable anticancer and antimicrobial properties by inducing Reactive Oxygen Species (ROS) generation, DNA damage, proteasome inhibition, mitochondrial dysfunction, and the recently identified pathway of cuproptosis. Furthermore, advancements in nanotechnology and targeted delivery systems have improved the specificity, bioavailability, and therapeutic efficacy of copper-based agents while minimising systemic toxicity. Despite challenges related to stability and controlled delivery, copper therapeutics represent a highly versatile and cost-effective approach for combating cancer, multidrug-resistant infections, and redox-associated diseases. This review finds its necessity for a comprehensive understanding of copper metabolism, biological functions and its therapeutic applications. It highlights the growing significance of copper-based therapeutics in next-generation medicinal chemistry and translational biomedical research.