Although many antifungal agents are available in clinical treatment, increasing resistance of fungi, especially Candida species, to the available drugs requires the development of new safe and non-toxic compounds with novel modes of action as effective treatment against resistant microorganisms. Cobalt complexes are very interesting and attractive as potential candidates with antimicrobial activity. Their therapeutic uses as antiviral, antibacterial antifungal, antiparasitic, antitumour, transferrin transporters, and anti-inflammatory agents are being intensively investigated. In this study we examined the antifungal activity of Co(III) complexes with diamine chelate ligands against a broad spectrum of Candida species. Minimum inhibitory concentration was determined by the microbroth dilution method and with serial passaging assay; the synergistic antimicrobial activity of the tested complexes combined with two antifungal drugs (ketoconazole and amphotericin B) was made by checkerboard assay. The effects of Co(III) complexes on yeast cell morphology were studied by optical and transmission electron microscopy. The mode of action of Co(III) complexes on the yeast cell wall (sorbitol assay) and cell membrane (ergosterol assay) were investigated. The cytotoxic effects of the tested compounds on red blood cells and the human keratinocyte (HaCaT) cell line were also evaluated. The analyzed compounds revealed significant antifungal activity for selected strains of Candida species; [CoCl₂(dap)₂]Cl (1) and [CoCl₂(en)₂]Cl (2) were more effective than ketoconazole. Its probable mechanism of action did not involve the cell wall or ergosterol binding. However, the checkerboard assay showed, that the antifungal activity of ketoconazole increased in combination with the tested complexes of Co(III). Our results suggest that both diamine complexes with Co(III) analogs caused damage to mitochondrial membrane or the membrane of the endoplasmic reticulum. The effect was observed by transmission electron microscope. Co(III) complexes with diamine chelate ligands are non-toxic at concentrations active against Candida species. This study provides new data on potential antifungal drugs, especially against Candida species.

Coordination chemistry offers much scope for the design of novel and therapeutic agents, including metallopharmaceuticals. The widespread use of metal complexes as effective pharmaceuticals, e.g. cancer therapeutic, anti-inflammatory, antidiabetic drugs or antimicrobial and diagnostic agents, demonstrates that the cytotoxicity of metal ions can be finely controlled via the appropriate choice of ligands. The successful targeting of radioisotopes again depends on the ligand design and metal oxidation state. The complexes of platinum, ruthenium, cobalt, copper and other d-block metal ions have been used in medicine for a long time but only recent advances have been made in understanding the molecular basis of mechanism of their action. Due to the above mentioned purpose, we decided to prepare a detailed description of target-based research, directed towards a design and application possibilities, with the known mechanisms of action of metal ion complexes in the broad sense of therapy definition. The review also covers the progress, limitations and challenges of the above-mentioned approaches and emphasizes the advantages of well known and new metallopharmaceuticals in medicine and pharmacy.

Ru(III) complexes with pyrazine derivatives: 2,3-bis(2-pyridyl)pyrazine (DPP), pyrazine-2-amidoxime (PAOX), pyrazine-2-thiocarboxamide (PTCA) and 2-amino-5-bromo-3-(methylamino)pyrazine (ABMAP) have been prepared. Characterization of the compounds was acquired using UV-Vis and FT-IR spectroscopy, elemental analysis, conductivity and electrochemical measurements as well as thermogravimetric studies. The ligand field parameters, Δ₀ (splitting parameter), B (Racah parameter of interelectronic repulsion) and β (nephelauxetic ratio) were calculated. The stabilities of the Ru(III) complexes have also been confirmed by spectrophotometric titration methods in acetonitrile and water solutions. The data showed that the examined compounds are stable both in solution and solid states, which was also confirmed by the values of their stability constants found. Moreover, the molecular structures of the complexes have been optimized using AM1 and PM3 methods and this supported octahedral geometry around the Ru(III) ion. The minimum inhibitory (MIC) and minimum bactericidal concentration (MBC) for synthesized complexes were studied against two Gram (+) bacteria, two Gram (−) bacteria and fungi – three reference strains of Candida albicans. The results show that [RuCl(PAOX)₂(OH₂)]Cl₂ display antifungal activity.

Antibiotic resistance is a global problem, and one promising solution to overcome this issue is using metallodrugs, which are drugs containing metal ions and ligands. These complexes are superior to free ligands in various characteristics including anticancer properties and mechanism of action. The pharmacological potential of metallodrugs can be modulated by the appropriate selection of ligands and metal ions. A good example of proper coordination is the combination of sulfonamides (sulfamerazine, sulfathiazole) with a ruthenium(III) ion. This work aimed to confirm that the activity of sulfonamides antibacterial drugs is initiated and/or stimulated by their coordination to an Ru(III) ion. The study determined the structure, electrochemical profile, CT-DNA affinity, and antimicrobial as well as anticancer properties of the synthesized complexes. The results proved that Ru(III) complexes exhibited better biological properties than the free ligands.

Cobalt coordination complexes are very attractive compounds for 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 Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration results revealed that anaerobic and microaerophilic bacteria were found to be the most sensitive; the serial passages assay presented insignificant increases in bacterial resistance to both compounds after 20 passages. The synergy assay showed a significant reduction in the MIC values of nalidixic acid when combined with Compounds (1) or (2). The assessment of cell damage by the complexes was performed using scanning electron microscopy, transmission electron microscopy, and confocal microscopy, which indicated cell membrane permeability, deformation, and altered cell morphology. DNA interaction studies of the Co(III) complexes with plasmid pBR322 using spectrophotometric titration methods revealed that the interaction between Complex (1) or (2) and DNA suggested an electrostatic and intercalative mode of binding, respectively. Furthermore, the DNA cleavage ability of compounds by agarose gel electrophoresis showed nuclease activity for both complexes. The results suggest that the effect of the tested compounds against bacteria can be complex.