Are the Co(III) complexes with diamine chelate ligands a response to new antifungal compounds?

Increasing resistance of fungi, especially Candida spp., successively has 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 mode 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 by elemental analysis, an ATR technique, and a scan method and sequentially tested against a wide range of Candida spp. strains. Analysed complexes exhibited strong antifungal activity against tested yeasts and were more effective than commercial antifungal drug, ketoconazole. However, antifungal activity of ketoconazole increased in combination with the tested complexes, what has been proven by checkerboard assay (the synergistic antimicrobial activity). The effects of Co(III) complexes on yeast cell morphology were also studied by transmission electron microscopy and showed changes in yeast cell morphology, indicating significant disruptions in the molecular machinery of cells. The complexes of Co(III) turned out also to be non-toxic in the concentrations tested for the antimicrobial activity, the cytotoxic effects of the tested compounds on red blood cells and the human keratinocyte (HaCaT) cell line were evaluated. This study provides new data on potential antifungal drugs, especially against Candida species.