Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth
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AuthorsSavic, Nada D.
Glisic, Biljana D.
Fromm, Katharina M.
Djuran, Milos I.
Article (Published version)
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Mononuclear silver(I) complexes with 1,7-phenanthroline (1,7-phen), [Ag(NO3-O,O') (1,7-phen-N7)(2)] (1) and [Ag(1,7-phen-N7)(2)]X, X = ClO4- (2), CF3SO3- (3), BF4- (4) and SbF6- (5) were synthesized and structurally characterized by NMR (H-1 and C-13), IR and UV-Vis spectroscopy and ESI mass spectrometry. The crystal structures of 1, 3 and 4 were determined by single-crystal X-ray diffraction analysis. In all these complexes, 1,7-phen coordinates to the Ag(I) ion in a monodentate fashion via the less sterically hindered N7 nitrogen atom. The investigation of the solution stability of 1-5 in DMSO revealed that they are sufficiently stable in this solvent at room temperature. Complexes 1-5 showed selectivity towards Candida spp. in comparison to bacteria, effectively inhibiting the growth of four different Candida species with minimal inhibitory concentrations (MIC) between 1.2 and 11.3 mu M. Based on the lowest MIC values and the lowest cytotoxicity against healthy human fibroblasts wit...h selectivity index of more than 30, the antifungal potential was examined in detail for the complex 1. It had the ability to attenuate C. albicans virulence and to reduce epithelial cell damage in the cell infection model. Induction of reactive oxygen species (ROS) response has been detected in C. albicans, with fungal DNA being one of the possible target biomolecules. The toxicity profile of 1 in the zebrafish model (Danio rerio) revealed improved safety and activity in comparison to that of clinically utilized silver(I) sulfadiazine.
Keywords:Silver(I) complexes / Antimicrobial activity / Cytotoxicity / Candida / Danio rerio
Source:European Journal of Medicinal Chemistry, 2018, 156, 760-773
- Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
- Synthesis of new metal complexes and investigation of their reactions with peptides (RS-172036)
- Microbial diversity study and characterization of beneficial environmental microorganisms (RS-173048)
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie
- Supra-MedChem"Balkans.Net SCOPES Institutional Partnership [IZ74Z0_160515]
- European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie 
- Serbian Academy of Sciences and Arts [F128]