Requirement for nonprotonated drug molecules in the direct lethal action of miconazole against Candida albicans |
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Authors: | William H Beggs |
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Institution: | (1) General Medical Research Service, Veterans Administration Medical Center, 55417 Minneapolis, MN, USA |
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Abstract: | At 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 6.5. Thus, in media of pH >6.5 most drug molecules are nonprotonated (MCZ). Conversely, at pH < 6.5 the majority are protonated and carry a positive charge (MCZH+). Our earlier work suggesting that MCZ is required for direct lethal action was tested further. In support of such a requirement, we established a minimal lethal concentration of MCZ (i.e. 5×10–6 M) that was relatively independent of pH, MCZ concentration, and MCZMCZH+ ratio. |
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Keywords: | antifungal imidazoles miconazole Candida albicans |
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