Azoles

The “azole” antifungals are a family of medications used to treat mycoses, or fungal infections.

Mycoses can be superficial, like on the skin or hair, or develop into systemic infections in immunodeficient people.

Antifungals work either through fungistatic action, meaning that they inhibit fungal growth, or through fungicidal action, meaning they kill the fungi.

Azoles are divided into two major families of antifungals: imidazoles and triazoles.

Most fungal cells have a tough outer cell wall and an inner cell membrane.

The cell membrane is mostly made of phospholipids with some sterol or modified steroid molecules mixed in.

Humans have cholesterol, while fungi have ergosterol.

Both sterol molecules help keep the cell membrane stable at a wide range of temperatures.

Now, the precursor to both molecules is lanosterol.

Fungi have a cytochrome p450 enzyme called fourteen-alpha-demethylase in their mitochondria and endoplasmic reticulums, which converts lanosterol to ergosterol.

Without ergosterol, the structure of the cell membrane will be disrupted.

This will cause membrane-bound proteins, like ion channels, to stop working properly.

The membrane also becomes fragile, which eventually leads to inhibition of fungal growth.

The azole antifungals include imidazoles, like clotrimazole, isoconazole, miconazole, butoconazole, fenticonazole, and ketoconazole; as well as triazoles like fluconazole, itraconazole and voriconazole.

The only difference between the two groups is the imidazoles contain an imidazole ring, while triazoles contain triazole rings.

These medications work by inhibiting the fourteen-alpha-demethylase enzyme.

However, they also inhibit human cytochrome P450 enzymes to a lesser degree.