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

J Inorg Biochem. 2020 Jul:208:111089. doi: 10.1016/j.jinorgbio.2020.111089. Epub 2020 May 6.

Abstract

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.

Keywords: Anti-Candida activity; Cytotoxicity; Filamentation inhibition; N-heterocycles; Synergy; Zinc(II) complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents* / chemical synthesis
  • Antifungal Agents* / chemistry
  • Antifungal Agents* / pharmacology
  • Candida albicans / growth & development*
  • Candida parapsilosis / growth & development*
  • Cell Line, Tumor
  • Coordination Complexes* / agonists
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Drug Synergism
  • Heterocyclic Compounds* / agonists
  • Heterocyclic Compounds* / chemistry
  • Heterocyclic Compounds* / pharmacology
  • Humans
  • Nystatin* / agonists
  • Nystatin* / chemistry
  • Nystatin* / pharmacology
  • Zinc* / agonists
  • Zinc* / chemistry
  • Zinc* / pharmacology

Substances

  • Antifungal Agents
  • Coordination Complexes
  • Heterocyclic Compounds
  • Nystatin
  • Zinc