Redefining Antifungal Treatment: The Innovation of Metal-Based Compounds

Fungal infections are a significant contributor to global morbidity and mortality, particularly among immunocompromised patients. With the increasing prevalence of drug-resistant strains, it has become imperative to identify alternative approaches. Metal ion coordination enhances drug efficacy through novel modes of action and may hinder resistance mechanisms. This article aims to identify gaps in the current metal-based antifungal therapy to guide research directions and facilitate drug development. Relevant metal complexes, together with their ligands, have been categorized according to their metal coordination and their activities highlighted. Most examples reported were found to be more effective against drug-resistant strains than non-coordinated ligands, thus establishing the importance of metal ion and co-ligand(s) nature, the influence of electron-withdrawing substituents on structure–activity relationships, and the unique structural features of Schiff bases. Although still at the preclinical phase, the in vitro efficacy of these examples suggests that metal-based drugs may represent a promising approach to overcoming antifungal resistance.