Zinc(II) complexes with aromatic nitrogen-containing heterocycles as antifungal agents: Synergistic activity with clinically used drug nystatin

Three novel Zn(II) complexes, [ZnCl2(qz)2] (1), [ZnCl2(1,5-naph)]n (2) and [ZnCl2(4,7-phen)2] (3), where qz is quinazoline, 1,5-naph is 1,5-naphthyridine and 4,7-phen is 4,7-phenanthroline, were synthesized by the reactions of ZnCl2 and the corresponding N-heterocyclic ligand in 1:2 molar ratio in ethanol at ambient temperature. The characterization of these complexes was done by NMR, IR and UV–Vis spectroscopy, and their crystal structures were determined by single-crystal X-ray diffraction analysis. Complexes 1 and 3 are mononuclear species, in which Zn(II) ion is tetrahedrally coordinated by two nitrogen atoms belonging to two qz or 4,7-phen ligands, respectively, and by two chloride anions, while complex 2 is a 1D coordination polymer that contains 1,5-naph as bridging ligand between two metal ions. In agar disc-diffusion assay, complexes 1–3 manifested good inhibitory activity against two investigated Candida strains (C. albicans and C. parapsilosis), while not inducing toxic effects on the healthy human fibroblast cell line (MRC-5). This activity was not fungicidal, as revealed by the broth microdilution assay, however complex 3 showed the ability to modulate Candida hyphae formation, which is an important process during infection and showed significant synergistic effect with clinically used antifungal polyene nystatin. Zinc(II) complex with 4,7-phenanthroline has the ability to interfere with fungal virulence factors and shows significant synergistic effect with clinically used antimicrobial agent nystatin, having the beneficial effect on both toxicity and the resistance potential of this drug. [Display omitted] •Three zinc(II) complexes with N-heterocycles were synthesized and characterized.•Zinc(II) complexes showed inhibitory activity against the Candida strains.•Complex 3 had the ability to modulate Candida hyphae formation.•Complex 3 showed significant synergistic effect with antifungal agent nystatin.