Cadmium(II) imidazole coordination complexes as selective antifungal agents against resistant Candida: Insights into...

Physicochemical and biological properties of four cadmium(II) coordination complexes with 4-methyl-5-imidazolecarboxaldehyde, differing in their inner-sphere halide anions: Cl^- (Cd-1), Br^- (Cd-2), I^- (Cd-3), or the PF₆^- counterion of the outer-sphere (Cd-4). The electrochemical characteristics of the tested compounds in Tris-HCl buffer were determined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), and nucleation was observed at the electrode surface. Isothermal titration calorimetry data revealed that the investigated complexes exhibit relatively high binding affinity for a specific site on bovine serum albumin, with the chloride complex achieving the highest value. These interactions occur at different stoichiometries, primarily driven by favorable enthalpic interactions. However, these binding interactions did not alter the protein's secondary structure. In vitro biological assays demonstrated potent and selective antifungal activity against Candida species, including fluconazole-resistant isolates, with MIC₅₀ values as low as 0.75 μM, while antibacterial effects were negligible. Cytotoxicity toward human A-549 and MCF-7 cell lines was moderate, yielding selectivity indices exceeding 10 for the most active antifungal coordination compound. Molecular docking studies involving CYP51 from Candida albicans and Candida glabrata suggest that this enzyme might be a molecular target of the described cadmium coordination compounds and that disruption of ergosterol biosynthesis might contribute to their observed antifungal activity. These findings highlight the potential of Cd(II)-imidazole derivative systems as selective antifungal agents and underscore the relevance of metal-ligand coordination in tuning bioactivity and protein-binding behavior.