Benzylideneindanones and Benzylidenebenzosuberones: Relationship between Structure, Antimycotic Activity and Acute Toxicity

Abstract

A series of <X_Underline>E</X_Underline>-2-benzylidene-1-indanones and <X_Underline>E</X_Underline>-2-benzylidene-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 µg/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 µg/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 models (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.

The in vitro Antimycotic Activity and Acute Toxicity of Third-Generation Bezylidenetetralones and Heteroarylidenetetralones

“…A two-tailed Anova model in SPSS for Windows (version 6.1.1) was used for statistical analysis. The values of the inhibitory concentrations (IC 50 ; Ìg/ml) were then determined from the graph for each compound or agent, as described earlier by us [6,7].…”

“…The LD 50 values were considered valid for any group of mice, per compound or agent, when the survival coefficient of variance for the particular dose used was within 3-5% [6,9].…”

“…and Trichosporon cutaneum, and compared to that of 6 commercially available antimycotic agents tested simultaneously [2][3][4][5][6].…”

Different packing motifs mediated by weak interactions and polymorphism in the crystal structures of five 2-(benzylidene)benzosuberone derivatives

“…Their biological activities include antitumour (e.g. Gautam et al, 2016: Dimmock et al, 1999, 2002, antimycotic (Al-Nakib et al, 1997) and antifungal (Gupta & Jain, 2015) properties. Their physical properties include nonlinear optical (Watson et al, 1993) and UV hypsochromic shifts and fluorescence effects (Fodor et al, 2011).…”

Direct Synthesis and Antimicrobial Evaluation of Structurally Complex Chalcones

“…[13] Also, indanone chalcones (6) have gained much importance due to their highly significant biological activities which have been shown to include antifungal, [14] anti-cholinergic, [15] anti-oxidant [16] and anticancer effectiveness (Figure 1). [17][18] In addition and relevant to [19] Encouraged by the unusually potent biological activities of chalcones and their congeners, we were motivated to develop a new, and decidedly simpler, synthetic process for making these compounds more readily available.…”