PUBLICATION
Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection
- Authors
- Pavic, A., Savić, N.D., Glišić, B.Đ., Crochet, A., Vojnovic, S., Kurutos, A., Stanković, D.M., Fromm, K.M., Nikodinovic-Runic, J., Djuran, M.I.
- ID
- ZDB-PUB-190406-21
- Date
- 2019
- Source
- Journal of inorganic biochemistry 195: 149-163 (Journal)
- Registered Authors
- Keywords
- Candida albicans, DNA interaction, Danio rerio, Infection model, Phenanthroline, Silver(I) complexes
- MeSH Terms
-
- Animals
- Antifungal Agents/chemical synthesis
- Antifungal Agents/therapeutic use*
- Antifungal Agents/toxicity
- Candida albicans/drug effects*
- Candidiasis/drug therapy*
- Cell Proliferation/drug effects
- Coordination Complexes/chemical synthesis
- Coordination Complexes/therapeutic use*
- Coordination Complexes/toxicity
- Microbial Sensitivity Tests
- Phenanthrolines/chemical synthesis
- Phenanthrolines/therapeutic use*
- Phenanthrolines/toxicity
- Reactive Oxygen Species/metabolism
- Silver/chemistry
- Zebrafish/embryology
- PubMed
- 30952084 Full text @ J. Inorg. Biochem.
Citation
Pavic, A., Savić, N.D., Glišić, B.Đ., Crochet, A., Vojnovic, S., Kurutos, A., Stanković, D.M., Fromm, K.M., Nikodinovic-Runic, J., Djuran, M.I. (2019) Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection. Journal of inorganic biochemistry. 195:149-163.
Abstract
Five novel silver(I) complexes with 4,7-phenanthroline (4,7-phen), [Ag(NO3-O)(4,7-phen-μ-N4,N7)]n (1), [Ag(ClO4-О)(4,7-phen-μ-N4,N7)]n (2), [Ag(CF3COO-O)(4,7-phen-μ-N4,N7)]n (3), [Ag2(H2O)0.58(4,7-phen)3](SbF6)2 (4) and {[Ag2(H2O)(4,7-phen-μ-N4,N7)2](BF4)2}n (5) were synthesized, structurally elucidated and biologically evaluated. These complexes showed selectivity towards Candida spp. in comparison to the tested bacteria and effectively inhibited the growth of four different Candida species, particularly of C. albicans strains, with minimal inhibitory concentrations (MICs) in the range of 2.0-10.0 μM. In order to evaluate the therapeutic potential of 1-5, in vivo toxicity studies were conducted in the zebrafish model. Based on the favorable therapeutic profiles, complexes 1, 3 and 5 were selected for the evaluation of their antifungal efficacy in vivo using the zebrafish model of lethal disseminated candidiasis. Complexes 1 and 3 efficiently controlled and prevented fungal filamentation even at sub-MIC doses, while drastically increased the survival of the infected embryos. Moreover, at the MIC doses, both complexes totally prevented C. albicans filamentation and rescued almost all infected fish of the fatal infection outcome. On the other side, complex 5, which demonstrated the highest antifungal activity in vitro, affected the neutrophils occurrence of the infected host, failed to inhibit the C. albicans cells filamentation and showed a poor potential to cure candidal infection, highlighting the importance of the in vivo activity evaluation early in the therapeutic design and development process. The mechanism of action of the investigated silver(I) complexes was related to the induction of reactive oxygen species (ROS) response in C. albicans, with DNA being one of the possible target biomolecules.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping