Biosynthesis of ergosterol as a relevant molecular target of metal-based antiparasitic and antifungal compounds

Trypanosomatid parasites and fungi cause highly prevalent diseases. Ergosterol plays a crucial role in the structure and normal function of the membrane of these microorganisms. It is absent in mammals. Many enzymes of the ergosterol biosynthesis route have been recognized as molecular targets for drugs. Currently, a variety of organic drugs that interfere with sterol biosynthesis are employed to treat fungal infections, and some of them have been proposed as potential treatments for trypanosomiasis. Coordinating these organic drugs to metal ions may positively impact the biological performance by altering relevant physicochemical properties. Additionally, their organometallic derivatization could improve the effectiveness. This comprehensive review aims to highlight the considerable promise of metal-based compounds as inhibitors of essential pathways or key enzymes of these microorganisms, with focus on the ergosterol biosynthesis pathway. Additionally, bioactive metal compounds that have demonstrated experimental efficacy in acting on enzymes within this pathway although not designed for this purpose were included. The current state of the art demonstrates the impressive but still underexplored potential of these metal-based compounds for treating fungal and trypanosomatid infections.