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

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

Structure to antimycotic activity of benzylid enechromanones against 6 miconazole-resistant pathogenic yeasts in vitro

Fifty-five new compounds belonging to the naturally occurring benzylidene chromanones were synthesised and their activity against the important human pathogenic yeasts Cryptococcus neoformans, Candida spp., Trichosporon cutaneum and Torulopsisgh brata was assessed in vitro using a microtitre technique. These yeasts had already been found resistant to miconazole, at a minimum inhibitory concentration [MIC] of 100 micro g/ml or more The structural differences between the molecules of the new compounds, such as their three dimensional shape, the presence of oxygen or sulphur hetero-atoms, or a cyclic bridge, were studied to establish models for their structure-to-antimycotic activity. Twenty-eight of the compounds were found active against the tested yeasts and had an MIC of 6 micro g/ml. There was a heterogeneity in the response of the yeasts to the active compounds, which could be linked to structural factors in C. neoformans

Antimycotic activity and acute toxicity of benzopyranopyrans and related compounds

A series of 39 new benzopyranopyrans and related compounds were synthesised and their antimycotic activity in vitro was evaluated against 4 species of human pathogenic yeasts which were insensitive to miconazole, isoconazole and tolnaftate. The minimum inhibitory concentrations [MICs] of these commercial compounds ranged between 50 and 150 micro g/ml. Of the new compounds, 15 were active against 5 strains of Cryptococcus neofor-mans, while 9 more were active against 3 of these strains with an MIC of 6 micro g/ml or lower. Similar MICs were shown by 5 compounds which were active against Candida albicans and 3 which were active against Trichosporon cutaneum. All the active compounds were found to be less toxic than the 3 commercial antimycotics, as judged by their LD[50] values in mice. A number of deductions were made regarding the structural variations which resulted in the heterogeneity of response shown by the strains of C. neoformans tested in this series