Are the Co(III) Complexes with Diamine Chelate Ligands a Response to New Antifungal Compounds? ^†

Abstract

Increasing resistance of fungi, especially Candida spp., has successively reduced the already short list of effective antifungal drugs used in clinical therapy. Thus there is an urgent need for new, non-toxic antifungals with novel modes of action. A very interesting and attractive group of compounds seems to be complexes of Co(III) with diamine chelate ligands due to their therapeutic uses as antiviral, antibacterial, antifungal, antiparasitic, or antitumor agents. Two Co(III) complexes with diamine chelate ligands ([CoCl₂(dap)₂]Cl (1) and [CoCl₂(en)₂]Cl (2)) (where dap = 1,3-diaminopropane, en = ethylenediamine) were synthesized and characterized using elemental analysis, an ATR technique, and a scan method and sequentially tested to evaluate the mode of action. The assessment of cell damage by the newly synthetized photosensitive fluorescein-labelled complex 1 ([Co(dap)₂FLU]Cl₂) was performed using fluorescent microscopy, which indicated cell membrane permeability and altered cell morphology. The study of the C. albicans survival in blood showed a slight reduction in the number of viable, colonizing cells in the sample compared to the results obtained for the substances with confirmed antifungal activity – ketoconazole. DNA cleavage ability of the Co(III) complexes using agarose gel electrophoresis against genomic DNA isolated from a C. albicans cells showed nuclease activity for both complexes. This study provides new data on potential antifungal drugs, especially against Candida species.