Cadmium(II) complexes with pyridine/dicarboxylic acid ligands as promising molecules for the treatment of oral candidiasis

Overgrowth of Candida spp., known for its strong adhesion to biotic and abiotic surfaces, makes treatment difficult in denture stomatitis. To address this challenge, two novel cadmium(II) complexes containing 2,5-pyridinedicarboxylic acid (H₂L) (complex 1 [Cd(HL)(H₂O)(DMSO)I]₂ and [Cd(HL)(H₂O)(bipy)I] complex 2), were synthesized and fully characterized by X-ray diffractometry, HRMS-ESI (+) spectrometry, ¹H and ¹³C NMR, FT-IR and elemental analysis. These complexes were evaluated for their antifungal, antibiofilm, hemolytic, and mutagenic properties. The interaction of these complexes with established antifungal agents was also investigated. Both complexes demonstrated remarkable antifungal activity, particularly against C. albicans and C. krusei, with MIC ranging from 62.5 (97.91 μM) to 0.48 (0.75 μM) μg/mL and MFC from 125 (195.82 μM) to 3.80 (5.95 μM) μg/mL. Furthermore, these complexes effectively inhibited C. krusei biofilm formation on prosthetic acrylic resin test specimens, with complex 2 showing superior activity. The complexes also displayed synergistic effects with fluconazole, furthermore, sorbitol assays have shown that cell wall is one of the targets of the tested complexes. Importantly, hemolysis assays indicated that the complexes were non-cytotoxic to human erythrocytes, and mutagenicity assays confirmed their non-mutagenic nature. These findings suggest that the synthesized cadmium(II) complexes, particularly complex 2, possess significant potential as therapeutic agents for the treatment of denture stomatitis and oral candidiasis in general.