Cinnamyl Schiff bases: synthesis, cytotoxic effects and antifungal activity of clinical interest

The aim of this study was to synthesize and investigate thein vitroantifungal properties of 23 cinnamyl Schiff bases. In addition, cytotoxic effects of such cinnamyl Schiff bases against human lung, kidney or red blood cells were also checked. The compounds were synthesized in a single-step, 2 min of reaction under microwave irradiation produced up to 97% yield. Six of the 23 cinnamyl Schiff bases possessed antifungal activities against strains ofCandida,Aspergillus,Fonsecaeaand, particularly,Cryptococcusspecies. Indeed, cinnamyl Schiff bases1and23exhibited minimum inhibitory concentration (MIC) values more than twofold lower than fluconazole (FCZ) against all theCryptococcus neoformansstrains (MIC = 1 center dot 33, 1 center dot 4 and 5 center dot 2 mu g ml(-1), respectively) andCryptococcus gattiistrains (MIC = 5 center dot 3, 2 center dot 8 and 9 center dot 2 mu g ml(-1), respectively) (12 strains of each species) while cinnamyl Schiff base11was as potent as FCZ against all strains from bothCryptococcusspecies. No significant cytotoxic effects were observed for Schiff bases against human lung, kidney or red blood cells, all presenting selective indexes higher than 10. In conclusion, this study revealed cinnamyl Schiff bases, especially1and23, as new lead anticryptococcal agents for the discovery of novel antifungal drugs. Significance and Impact of the Study The occurrence and severity of fungal infections have increased in recent decades due to resistance to available antifungal drugs and the appearance of new emerging pathogens. Thus, the search for new antifungal agents is mandatory. From a series of 23 cinnamyl Schiff bases, two compounds (1and23) were interrogated as new anticryptococcal agents without significant cytotoxicity against human lung, kidney or red blood cells. In turns, these new Schiff bases are lead compounds for the discovery of novel antifungal drugs.