Antifúngicos e Ergosterol

Ergosterol (ergosta-5,7,22-trien-3β-ol) is a sterol found in fungi (and named for ergot, a common name for the members of the fungal genus Claviceps from which ergosterol was first isolated). Ergosterol does not occur in plant or animal cells. It is a component of yeast and fungal cell membranes, serving the same function cholesterol serves in animal cells. Miconazole, itraconazole, and clotrimazole work in a different way, inhibiting synthesis of ergosterol from lanosterol. Ergosterol is a smaller molecule than lanosterol; it is synthesized by combining two molecules of farnesyl pyrophosphate, a 15-carbon-long terpenoid, into lanosterol, which has 30 carbons. Then, two methyl groups are removed, making ergosterol. The "azole" class of antifungal agents inhibit the enzyme that performs these demethylation steps in the biosynthetic pathway between lanosterol and ergosterol. Amphotericin B, an antifungal drug, targets ergosterol. It binds physically to ergosterol within the membrane, thus creating a polar pore in fungal membranes. This causes ions (predominantly potassium and protons) and other molecules to leak out, which will kill the cell.[8] Amphotericin B has been replaced by safer agents in most circumstances, but is still used, despite its side effects, for life-threatening fungal or protozoan infections. Like other allylamines, terbinafine inhibits ergosterol synthesis by inhibiting squalene epoxidase, an enzyme that is part of the fungal cell membrane synthesis pathway. Because terbinafine prevents conversion of squalene to lanosterol, ergosterol cannot be synthesized. This is thought to change cell membrane permeability, causing fungal cell lysis. Ergosterol is also present in the cell membranes of some protists, such as trypanosomes.[7] This is the basis for the use of some antifungals against West African sleeping sickness.