Category: biosynthesis
Ergosterol is the fungal-specific membrane sterol (analog of mammalian cholesterol). Selective antifungal toxicity targets enzymes unique to fungi: azoles (fluconazole, itraconazole, voriconazole, posaconazole, ketoconazole, miconazole, clotrimazole) inhibit CYP51 (sterol-14α-demethylase) — depleting ergosterol + accumulating toxic 14α-methylsterols. Off-target hit on mammalian CYP3A4 explains the massive DDI surface for systemic azoles (itraconazole 20× midazolam AUC, etc.). Terbinafine + allylamines inhibit squalene epoxidase upstream → toxic squalene buildup. Hydroxypyridones (ciclopirox) chelate Fe/Al cofactors of multiple fungal enzymes. Polyenes (amphotericin B, nystatin) bind ergosterol directly → membrane pores.