Fungal infections represent an increasing threat to a growing number of
immune- and medically compromised patients. Fungi, like humans, are eukaryotic
organisms and there are a limited number of selective targets that can be exploited for
antifungal drug development. This has also resulted in a very restricted number of
antifungal drugs that are clinically available for the treatment of superficial and
invasive fungal infections at the present time. Moreover, the utility of available
antifungals is limited by toxicity, drug interactions and the emergence of resistance,
which contribute to high morbidity and mortality rates. These limitations have created a
demand for the development of new antifungals, particularly those with novel
mechanisms of action.
The 1990s can be considered the “golden era” of antifungal drug development with
multiple big pharmaceutical companies actively engaged in the discovery and
development of novel antifungals. However, this has largely become stagnant since
then, and it has been two decades since the newest class of antifungal agents (the
echinocandins) reached the market. Overall, there are currently few classes of FDA-approved antifungal agents clinically used in the treatment of fungal infections. In this
chapter, we reviewed antifungal drugs and summarized their mechanisms of action,
pharmacological profiles, and susceptibility to specific fungi. Approved antimycotics
inhibit nucleic acid and microtubule synthesis, membrane ergosterol synthesis and cell
wall polymers’ synthesis, or sequestrate ergosterol. The experimental antifungal drugs
in clinical trials are also reviewed. We report sphingolipids and protein biosynthesis
inhibitors, which represent the most promising emerging antifungal therapies.
Keywords: Allylamines, Aureobasidin a, Azoles, Benzylamines, Cell wall, Echinocandins, Ergosterol, Flucytosine, Manogepix, Morpholines, Nucleosidepeptides, Olorofim, Polyenes, Sordarin, Tavaborole, Thiocarbamates, Triterpenes
