Benzylideneindanones and benzylidenebenzosuberones: relationship between structure, antimycotic activity and acute toxicity

ABSTRACT

A series of E-2-benzylidene-1-indanones and E-2-benzlididene-1-benzosuberones were synthesized to investigate their in vitro antifungal activity against 24 strains belonging to important human pathogenic yeasts, such as Cryptococcus neoformans, Candida spp. and Trichosporon cutaneum. These strains were shown to be resistant to miconazole and isoconazole. There was a diversity in response among the different strains. Many of the compounds tested were shown to have good activity and many had minimum inhibitory concentrations [MICs] of 6 micro g/ml or lower against most of the strains. The standard systemic and topical commercial drugs also showed a great degree of diversity, exhibiting MICs that ranged from 6 to >100 micro g/ml against the same yeast strains. The in vivo toxicity of the synthesized compounds tested by an acute toxicity procedure in mice [MFI strain] and the in vitro activity in HeLa cells suggests that most of the active compounds were of lower toxicity, while only a few were of a toxicity similar to that of the least toxic commercial antifungal agent investigated in our animal and cell culture modles [amphotericin B]. The relatively low LD50 and good MIC values of most of our compounds in comparison to the least toxic and most active commercial agents tested [amphotericin B and haloprogin, respectively] justifies the testing of these synthetic agents for further development