Chalcone Schiff bases disrupt cell membrane integrity of Saccharomyces cerevisiae and Candida albicans cells

Chalcones have a variety of cellular protective and regulatory functions that may have therapeutic potential in many diseases. In addition, they are considered to affect key metabolic processes in pathogens. Nevertheless, our current knowledge of the action of these compounds against fungal cell is scarce. Therefore, in this study, various substituted chalcone Schiff bases were investigated to reveal their cellular targets within the yeasts Saccharomyces cerevisiae and Candida albicans. First, their antifungal activities were determined via minimum inhibitory concentration method. Surprisingly, parent chalcone Schiff bases showed little or no antifungal activity, while the nitro-substituted derivatives were found to be highly active against yeast cells. Next, we set out to determine the cellular target of active compounds and tested the involvement of the cell wall and cell membrane in this process. Our conductivity assay confirmed that the yeast cell membrane was compromised, and that ion leakage occurred upon treatment with nitro-substituted chalcone Schiff bases. Therefore, the cell membrane came to the fore as a possible target for the active chalcone derivatives. We also showed that exogenous ergosterol added to the growth medium reduced the inhibitory effect of chalcones. Our findings open up new possibilities for the design of future antimicrobial agents based on this appealing backbone structure.