An Evaluation of the Acute in Vivo Toxicity of Benzylidenechroman-4-Ones, L-Thiobenzylidenechroman-4-Ones and Benzylidenetetralones

Abstract

A series of new compounds were evaluated for acute in vivo toxicity. Their synthesis and antifungal activity have previously been described by us. The naturally occurring class of compounds to which they belong - the benzylidenechroman-4-ones - have been identified as a potential source of new antifungal agents. These compounds were found to be less toxic, as judged by acute toxicity, than existing commercially available antifungals. A number of conclusions can be drawn about the relationship of structural changes in this series of compounds to increases or decreases in acute toxicity.

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

“…The cells which were originally hospital isolates from different hospitals in Kuwait and Ireland were maintained by routine subculture on subaroid solid media and were classified using conventional methods [2,4,14]. The level of DMSO in any well did not exceed 2.5% (v/v), which was found to be non-inhibitory to fungal growth in control wells [2][3][4]7]. For assessment of the level of the antimycotic activity of the compounds prepared in this investigation, 6 commercial antimycotic agents were also tested simultaneously using the same experimental conditions.…”

“…A double dilution method within the concentration range of 0.8-100 Ìg/ml was used against 24 strains of C. neoformans, Candida spp. and T. cutaneum, employing the procedure reported earlier [2][3][4]7]. The cells which were originally hospital isolates from different hospitals in Kuwait and Ireland were maintained by routine subculture on subaroid solid media and were classified using conventional methods [2,4,14].…”

“…Although these first-generation E-2-benzylidene-1-tetralones were shown to ex- hibit very low toxicity in vivo [3], their in vitro activity against some pathogenic yeasts was found to be discouraging [2][3][4]. When the new aldol condensation, performed in ethanolic sodium hydroxide at 0°C, was utilised to synthesise another generation of E-2-benzylidine-or E-2-heteroarylidene-1-tetralones (compounds 1-12 or 13-19, respectively), the condensation products obtained also had the E configuration ( fig.…”

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

“…The toxicities of the compounds prepared were investigated both in vitro in a HeLa cell line [7,8] as well as by an acute toxicity procedure in MFI mice [3,[7][8][9], and the results were compared with those of 6 commercial antimycotic agents, tested similarly.…”