Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection

Pavic, Aleksandar; Savić, Nada D.; Glišić, Biljana Đ.; Crochet, Aurélien; Vojnovic, Sandra; Kurutos, Atanas; Stanković, Dalibor M.; Fromm, Katharina M.; Nikodinovic-Runic, Jasmina; Djuran, Miloš I.

doi:10.1016/j.jinorgbio.2019.03.017

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Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection

Pavic, Aleksandar Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia
Savić, Nada D. University of Kragujevac, Faculty of Science, Department of Chemistry, Kragujevac, Serbia
Glišić, Biljana Đ. University of Kragujevac, Faculty of Science, Department of Chemistry, Kragujevac, Serbia
Crochet, Aurélien Department of Chemistry, University of Fribourg, Switzerland
Vojnovic, Sandra Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia
Kurutos, Atanas Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria
Stanković, Dalibor M. The Vinča Institute of Nuclear Sciences, Belgrade, Serbia
Fromm, Katharina M. Department of Chemistry, University of Fribourg, Switzerland
Nikodinovic-Runic, Jasmina Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia
Djuran, Miloš I. Serbian Academy of Sciences and Arts, Belgrade, Serbia

01.06.2019

Published in:

Journal of Inorganic Biochemistry. - 2019, vol. 195, p. 149–163

English 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.

Faculty

Faculté des sciences et de médecine

Department

Département de Chimie

Language