Аннотация:Hydrolytic enzymes secreted by fungi seem to be promising among a number of targets for the action of antifungal agents suppressing fungal growth. Taking these into account, in this work we have investigated the possibility of targeted use of various ionophores as antifungal agents by inhibiting hydrolytic enzymes of fungi. Based on our analysis of literary, 17 ionophores were selected as potential inhibitors of fungal enzymes’ activity or pathways associated with their synthesis and functioning. The interactions of selected ionophores with 9 fungal hydrolytic enzymes, including cellulases, amylases and proteases were studied in silico using the molecular docking method and 4 ionophores amphotericin B, epigallocatechin gallate, monensin and valinomycin were chosen as the most potent inhibitors for subsequent experimental studies. Next, the effect of these ionophores on the catalytic characteristics of hydrolytic enzymes was assessed and two ionophores valinomycin (Ki = 21 – 612 μM) and monensin (Ki = 16 – 492 μM) were found to be the most effective inhibitors. Further study of their antifungal efficacy against cells of different filamentous fungi allowed to reveal high antifungal action efficiency of valinomycin (IC50 = 0.11 – 8.99 μM) and monensin (IC50 = 0.28 – 10.4 μM) against fungi of the genera Fusarium, Aspergillus and Trichoderma. Ionophores considered in this study have great potential for use as effective antifungal agents or additives to antifungal drugs in various fields, including food and agriculture sector, and medicine.
