Antifungal toxicity of linear geranylphenol. Influence of oxigenate substituents.

Twenty four linear geranylphenols were evaluated for their antifungal properties against ATCC and clinical isolates of Candida albicans and Cryptococcus neoformans. For the analysis of their antifungal behavior the compounds were grouped into two series: (i) compounds with only one geranyl substituent on the benzene ring and (ii) compounds with two geranyl moieties on the benzene ring. Results showed that compounds of series (i) present better antifungal activities than those of series (ii). In addition, within group (i) all compounds showed better activities against C. neoformans than against C. albicans which can be easily verified by comparing MIC100 or MIC50 of each compound against both fungi. Di- (10 and 11) and tri-hydroxy (3 and 4) compounds showed significant anti-cryptoccocal activity, being 3, 10 and 11 highly active with MIC100 or MIC50 = 3.9 μg/mL similar to the standard drug amphotericin B. Moreover, when evaluating the toxicity of compounds 6, 10 and 11 on the HDF cell line (human dermal fibroblasts), results were obtained with IC50 values > 100 μM, considered as non-toxic for the cell. This indicates that the toxicity of the analyzed compounds is selective towards fungi, which makes them a very attractive family for the development of future drugs.