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Effects of griseofulvin on dermatophytes Ronald, William Pattison

Abstract

The site of action of griseofulvin, a drug which is reported to be fungistatic in nature, has been under study for some time. As yet though, there is still a great deal of uncertainty as to which observed effects are primary and which are secondary. In the study reported here, initial experiments were involved with effects of griseofulvin on oxygen uptake, in correlation with cell starvation. The effects of the drug on glucose oxidation also were studied. Definite alterations were noted in both of these areas. Further investigations were carried out, utilizing cell-free extracts and techniques for measurement of dehydrogenases, but these proved unsuccessful. Amino acid metabolism also was surveyed but no evidence of any alteration was observed. Attempts to produce protoplasts from dermatophytes were successful, and utilizing these structures, investigations into the effects of griseofulvin on cytoplasmic membrane permeability and on cell wall resynthesis, were carried out. In both cases the alterations were small and appeared to be secondary in nature. In the final study, purified cell walls of organisms grown in the presence and absence of griseofulvin, were compared on the basis of amino acid, amino sugar, and sugar content. No differences were observed in these preparations. In addition, no evidence was found to show that griseofulvin wlis incorporated into cell walls. It was concluded that griseofulvin may possibly affect the enzymes involved in the synthesis of the substrates of endogenous respiration, or the mechanisms controlling these enzymes. It was also concluded that the drug's site of action is probably on or near the cytoplasmic membrane, and by inference that the biochemical site may be in the area of purine and pyrimidine metabolism.

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