What is the mechanism by which azole antifungals work?

Azole antifungals primarily function by inhibiting the synthesis of ergosterol, an essential component of fungal cell membranes. Ergosterol plays a critical role in maintaining membrane integrity and fluidity, similar to cholesterol in human cell membranes. By blocking the enzyme lanosterol 14α-demethylase, which is necessary for converting lanosterol to ergosterol, azole antifungals disrupt the formation of the fungal cell membrane. This can lead to increased permeability, resulting in cell lysis and ultimately the death of the fungal cell.

The effectiveness of azoles is particularly important in treating systemic and superficial fungal infections because they target an essential biosynthetic pathway that is not present in human cells, thus minimizing harm to the host while effectively combating the infection.