Requirement for nonprotonated drug molecules in the direct lethal action of miconazole against Candida albicans.

At greater than or equal to 10(-5) M, miconazole (MCZ) can exert a direct physicochemical cell-damaging lethal action against logarithmic phase yeasts of Candida albicans. The imidazole moiety of MCZ has a pKa approximately 6.5. Thus, in media of pH greater than 6.5 most drug molecules are nonprotonated (MCZ degrees). Conversely, at pH less than 6.5 the majority are protonated and carry a positive charge (MCZH+). Our earlier work suggesting that MCZ degrees is required for direct lethal action was tested further. In support of such a requirement, we established a minimal lethal concentration of MCZ degrees (i.e. 5 x 10(-6) M) that was relatively independent of pH, MCZ concentration, and MCZ degrees:MCZH+ ratio.