Mode of action of clotrimazole

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Abstract
Clotrimazole, a synthetic antifungal agent, was fungicidal to growing cultures of one strain of Candida albicans. Cultures treated with the drug were osmotically stable. It had no effect on the respiratory activity of intact C. albicans cells or their isolated mitochondria with exogenous NADH and succinate as substrates. Studies with radioactive precursors revealed that clotrimazole inhibited synthesis of both protein and RNA by intact cells to a greater extent than that of DNA, lipid and wall polysaccharides. However, even with higher levels of the drug, the effect on endogenous or poly U-directed polypeptide synthesis by cell-free extracts was consistently negative. The minimum fungicidal concentration of the drug caused a marked enhancement of leakage of intracellular phosphorus compounds into the ambient medium with concomitant breakdown of cellular nucleic acids. Acceleration of K-efflux in treated cells also occurred to the corresponding extent. Both of these events began rapidly and extensively after the addition of the drug. Thus it is presumed that clotrimazole acts primarily by damaging the permeability barrier, possibly through reaction with the cell membrane, of sensitive organisms.

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