Volume 103, Number 2, 91-94, DOI: 10.1007/BF00441264

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

William H. Beggs

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Abstract

At ge10–5 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 sim 6.5. Thus, in media of pH >6.5 most drug molecules are nonprotonated (MCZcompfn). Conversely, at pH < 6.5="" the="" majority="" are="" protonated="" and="" carry="" a="" positive="" charge="">+). Our earlier work suggesting that MCZcompfn is required for direct lethal action was tested further. In support of such a requirement, we established a minimal lethal concentration of MCZcompfn (i.e. 5×10–6 M) that was relatively independent of pH, MCZ concentration, and MCZcompfnratioMCZH+ ratio.

Key words  antifungal imidazoles - miconazole -  Candida albicans

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