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

Authorized Users Only
2019
Authors
Pavić, Aleksandar B.
Savić, Nada D.
Glišić, Biljana Đ.
Crochet, Aurélien
Vojnović, Sandra
Kurutos, Atanas
Stanković, Dalibor M.
Fromm, Katharina M.
Nikodinović-Runić, Jasmina
Đuran, Miloš I.
Article (Published version)
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Abstract
Five novel silver(I) complexes with 4,7-phenanthroline (4,7-phen), [Ag(NO 3 -O)(4,7-phen-μ-N4,N7)] n (1), [Ag(ClO 4 -О)(4,7-phen-μ-N4,N7)] n (2), [Ag(CF 3 COO-O)(4,7-phen-μ-N4,N7)] n (3), [Ag 2 (H 2 O) 0.58 (4,7-phen) 3 ](SbF 6 ) 2 (4) and {[Ag 2 (H 2 O)(4,7-phen-μ-N4,N7) 2 ](BF 4 ) 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 a...nd 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. © 2019 Elsevier Inc.

Keywords:
Silver(I) complexes / Phenanthroline / DNA interaction / Candida albicans / Dania rerio / Infection model
Source:
Journal of Inorganic Biochemistry, 2019, 195, 149-163
Funding / projects:
  • 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)
  • SupraMedChem@Balkans.Net SCOPES Institutional Partnership [IZ74Z0_160515]
  • Serbian Academy of Sciences and Arts [F128]
  • Strengthening of the MagBioVin Research and Innovation Team for Development of Novel Approaches for Tumour Therapy based on Nanostructured Materials (EU-621375)
Related info:
  • Referenced by
    https://vinar.vin.bg.ac.rs/handle/123456789/8130
  • Referenced by
    http://dx.doi.org/10.5517/ccdc.csd.cc2127yb

DOI: 10.1016/j.jinorgbio.2019.03.017

ISSN: 0162-0134; 1873-3344

PubMed: 30952084

WoS: 000469408500016

Scopus: 2-s2.0-85063663119
[ Google Scholar ]
14
12
URI
https://vinar.vin.bg.ac.rs/handle/123456789/8127
Collections
  • Radovi istraživača
Institution/Community
Vinča
TY  - JOUR
AU  - Pavić, Aleksandar B.
AU  - Savić, Nada D.
AU  - Glišić, Biljana Đ.
AU  - Crochet, Aurélien
AU  - Vojnović, Sandra
AU  - Kurutos, Atanas
AU  - Stanković, Dalibor M.
AU  - Fromm, Katharina M.
AU  - Nikodinović-Runić, Jasmina
AU  - Đuran, Miloš I.
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8127
AB  - Five novel silver(I) complexes with 4,7-phenanthroline (4,7-phen), [Ag(NO 3 -O)(4,7-phen-μ-N4,N7)] n (1), [Ag(ClO 4 -О)(4,7-phen-μ-N4,N7)] n (2), [Ag(CF 3 COO-O)(4,7-phen-μ-N4,N7)] n (3), [Ag 2 (H 2 O) 0.58 (4,7-phen) 3 ](SbF 6 ) 2 (4) and {[Ag 2 (H 2 O)(4,7-phen-μ-N4,N7) 2 ](BF 4 ) 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. © 2019 Elsevier Inc.
T2  - Journal of Inorganic Biochemistry
T1  - Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection
VL  - 195
SP  - 149
EP  - 163
DO  - 10.1016/j.jinorgbio.2019.03.017
ER  - 
@article{
author = "Pavić, Aleksandar B. and Savić, Nada D. and Glišić, Biljana Đ. and Crochet, Aurélien and Vojnović, Sandra and Kurutos, Atanas and Stanković, Dalibor M. and Fromm, Katharina M. and Nikodinović-Runić, Jasmina and Đuran, Miloš I.",
year = "2019",
abstract = "Five novel silver(I) complexes with 4,7-phenanthroline (4,7-phen), [Ag(NO 3 -O)(4,7-phen-μ-N4,N7)] n (1), [Ag(ClO 4 -О)(4,7-phen-μ-N4,N7)] n (2), [Ag(CF 3 COO-O)(4,7-phen-μ-N4,N7)] n (3), [Ag 2 (H 2 O) 0.58 (4,7-phen) 3 ](SbF 6 ) 2 (4) and {[Ag 2 (H 2 O)(4,7-phen-μ-N4,N7) 2 ](BF 4 ) 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. © 2019 Elsevier Inc.",
journal = "Journal of Inorganic Biochemistry",
title = "Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection",
volume = "195",
pages = "149-163",
doi = "10.1016/j.jinorgbio.2019.03.017"
}
Pavić, A. B., Savić, N. D., Glišić, B. Đ., Crochet, A., Vojnović, S., Kurutos, A., Stanković, D. M., Fromm, K. M., Nikodinović-Runić, J.,& Đuran, M. I.. (2019). Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection. in Journal of Inorganic Biochemistry, 195, 149-163.
https://doi.org/10.1016/j.jinorgbio.2019.03.017
Pavić AB, Savić ND, Glišić BĐ, Crochet A, Vojnović S, Kurutos A, Stanković DM, Fromm KM, Nikodinović-Runić J, Đuran MI. Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection. in Journal of Inorganic Biochemistry. 2019;195:149-163.
doi:10.1016/j.jinorgbio.2019.03.017 .
Pavić, Aleksandar B., Savić, Nada D., Glišić, Biljana Đ., Crochet, Aurélien, Vojnović, Sandra, Kurutos, Atanas, Stanković, Dalibor M., Fromm, Katharina M., Nikodinović-Runić, Jasmina, Đuran, Miloš I., "Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection" in Journal of Inorganic Biochemistry, 195 (2019):149-163,
https://doi.org/10.1016/j.jinorgbio.2019.03.017 . .

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