Abstract:
The development of antifungal drugs encounters a significant challenge due to the close phylogenetic relationship between
fungi and mammals, both being eukaryotic organisms that share many similar cellular and molecular processes. The
toxicity of antifungal compounds is bilaterally distributed, complicating the development of highly selective therapeutic
agents. The four classes of antifungals for treating invasive fungal infections—polyene macrolides, azoles, pyrimidine
analogs, and echinocandins—offer therapeutic benefits but also have limitations regarding their spectrum of activity,
route of administration, drug interactions, toxicity, limited ability to target multiple fungal sites, resistance to
monotherapy, and short half-life. These limitations, alongside the emergence of antifungal-resistant strains and new multiresistant
species like Candida auris, contribute to inadequate therapeutic effects and rising mortality rates. Research into
the pathogenic mechanisms of potentially invasive fungi, particularly their nutritional vulnerability to iron, is driven by
the need to diversify antifungal „armamentarium”, as iron is crucial for their survival and virulence in the host. The
challenge of developing new antifungal drugs has shifted research toward improving existing ones. This promising
approach combines conventional therapies with strategies targeting iron acquisition, potentially lowering therapeutic
doses and addressing multiple targets, which could slow the development of resistance.
