The in vitro antimycotic activity and acute toxicity of third-generation bezylidenetetralones and heteroarylidenetetralones

Objectives: A new series of E-2-arylmethylene-1-tetralones and E-2-heteroarylmethylene-1-tetralones (third generation) were designed as potential antimycotic agents against human pathogenic yeasts. Methods: The new compounds were obtained by aldol condensation of 1-tetralone with the appropriately substituted aldehydes in either acid- or base-catalysed conditions. These compounds were tested for their in vitro antimycotic activity against 24 strains of Cryptococcus neoformans, Candida spp. and Trichosporon cutaneum by a microtitre well technique in a liquid casitone medium, using a double dilution method. The toxicity of the new compounds was determined in vitro in cultured HeLa cells, in HeLa growth medium and in vivo in MFI mice. Results: Nineteen new E-2-benzylidine-1-tetralones were prepared, and 16 of the tested compounds showed superior antimycotic activity when compared to the first-generation E-2-benzylidine-1-tetralones synthesised previously. Twelve of these third-generation compounds were more active against different strains of yeasts than 6 commercial antimycotic agents similarly tested. An in vitro toxicity study and an in vivo acute toxicity study in MA mice showed that these compounds were severalfold less toxic than most of the commerical antimycotics, with 4 being comparable to or less toxic than the least toxic of the commercial agents (amphotericin B) tested by the same procedures. Conclusions: Twelve members of this new E-2-benzylidine-1-tetralone class of compounds are promising candidates for antimycotic agents worthy of further investigation. Copyright (C) 2001 S. Karger AG, Basel.