Allylamines, Benzylamines, and Fungal Cell Permeability: A Review of Mechanistic Effects and Usefulness against Fungal Pathogens

Allylamines, naftifine and terbinafine, and the benzylamine, butenafine, are antifungal agents with activity on the fungal cell membrane. These synthetic compounds specifically inhibit squalene epoxidase, a key enzyme in fungal sterol biosynthesis. This results in a deficiency in ergosterol, a major fungal membrane sterol that regulates membrane fluidity, biogenesis, and functions, and whose damage results in increased membrane permeability and leakage of cellular components, ultimately leading to fungal cell death. With the fungal cell membrane being predominantly made up of lipids including sterols, these lipids have a vital role in the pathogenesis of fungal infections and the identification of improved therapies. This review will focus on the fungal cell membrane structure, activity of allylamines and benzylamines, and the mechanistic damage they cause to the membrane. Furthermore, pharmaceutical preparations and clinical uses of these drugs, mainly in dermatophyte infections, will be reviewed.