Proton translocating ATPase mediated fungicidal activity of eugenol and thymol

Eugenol (1) and thymol (2) exhibit excellent fungicidal activity against pathogenic yeasts, including isolates resistant to azoles. The rapid irreversible action of compound-1 and compound 2 on fungal cells suggested a membrane-located target for their action. We investigated their effect on H⁺-ATPase mediated H⁺-pumping by various Candida species. Both compounds inhibit H⁺-ATPase activity at their respective MIC values — 500 and 100 μg/ml. Glucose stimulated H⁺-extrusion was also inhibited significantly by compound 1 and compound 2. Inhibition of H⁺-ATPase leads to intracellular acidification and cell death. Inhibition of cell growth and H⁺-efflux by test compounds suggests that their antifungal properties are related to their inhibitory effects on H⁺-ATPase.