Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection
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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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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 modelSource:
Journal of Inorganic Biochemistry, 2019, 195, 149-163Funding / projects:
- Synthesis of new metal complexes and investigation of their reactions with peptides (RS-MESTD-Basic Research (BR or ON)-172036)
- Microbial diversity study and characterization of beneficial environmental microorganisms (RS-MESTD-Basic Research (BR or ON)-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-FP7-621375)
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
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VinčaTY - 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 . .