What is the mechanism of action for azole antifungals?

Azole antifungals function primarily by inhibiting lanosterol demethylase, which is an essential enzyme in the ergosterol biosynthesis pathway. Ergosterol is a crucial component of fungal cell membranes, similar to cholesterol in human cells. By obstructing the action of lanosterol demethylase, azoles prevent the conversion of lanosterol to ergosterol, leading to a disruption in membrane integrity and function. This ultimately impairs cell growth and replication of the fungus.

Because ergosterol is vital for maintaining the structural and functional integrity of the fungal cell membrane, its depletion due to the inhibited enzymatic process results in increased membrane permeability and, consequently, fungal cell death. This mechanism specifically targets fungal cells while sparing human cells, making azoles effective antifungal agents.

Other mechanisms such as inhibiting squalene epoxidase or targeting cell wall synthesis are associated with different classes of antifungal agents, such as allylamines or echinocandins, respectively, which underscores the distinct and targeted approach of azole antifungals in combating fungal infections.