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, AleksandarSavić, Nada D.
Glišić, Biljana
Crochet, Aurelien
Vojnović, Sandra
Kurutos, Atanas
Stanković, Dalibor
Fromm, Katharina M.
Nikodinović-Runić, Jasmina
Djuran, Milos
Article (Published version)
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Show full item recordAbstract
Five novel silver(I) complexes with 4,7-phenanthroline (4,7-phen), [Ag(NO3-O)(4,7-phen-mu-N4,N7)](n) (1), [Ag(ClO4-O)(4,7-phen-mu-N4,N7)](n) (2), [Ag(CF3COO-O)(4,7-phen-mu-N4,N7)](n) (3), [Ag-2(H2O)(0.58)(4,7-phen)(3)](SbF6)(2) (4) and {[Ag-2(H2O)(4,7-phen-mu-N4,N7)(2)](n)(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 mu M. 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.
Keywords:
Silver(I) complexes / Phenanthroline / Infection model / DNA interaction / Dania rerio / Candida albicansSource:
Journal of Inorganic Biochemistry, 2019, 195, 149-163Publisher:
- Elsevier Science Inc, New York
Funding / projects:
- SupraMedChem"Balkans.Net SCOPES Institutional Partnership [IZ74Z0_160515]
- Serbian Academy of Sciences and Arts [F128]
- Magbiovin project (FP7-ERAChairs-Pilot Call-2013) [621375]
- 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)
DOI: 10.1016/j.jinorgbio.2019.03.017
ISSN: 0162-0134
PubMed: 30952084
WoS: 000469408500016
Scopus: 2-s2.0-85063663119
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Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Pavić, Aleksandar AU - Savić, Nada D. AU - Glišić, Biljana AU - Crochet, Aurelien AU - Vojnović, Sandra AU - Kurutos, Atanas AU - Stanković, Dalibor AU - Fromm, Katharina M. AU - Nikodinović-Runić, Jasmina AU - Djuran, Milos PY - 2019 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1261 AB - Five novel silver(I) complexes with 4,7-phenanthroline (4,7-phen), [Ag(NO3-O)(4,7-phen-mu-N4,N7)](n) (1), [Ag(ClO4-O)(4,7-phen-mu-N4,N7)](n) (2), [Ag(CF3COO-O)(4,7-phen-mu-N4,N7)](n) (3), [Ag-2(H2O)(0.58)(4,7-phen)(3)](SbF6)(2) (4) and {[Ag-2(H2O)(4,7-phen-mu-N4,N7)(2)](n)(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 mu M. 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. PB - Elsevier Science Inc, New York T2 - Journal of Inorganic Biochemistry T1 - Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection EP - 163 SP - 149 VL - 195 DO - 10.1016/j.jinorgbio.2019.03.017 ER -
@article{ author = "Pavić, Aleksandar and Savić, Nada D. and Glišić, Biljana and Crochet, Aurelien and Vojnović, Sandra and Kurutos, Atanas and Stanković, Dalibor and Fromm, Katharina M. and Nikodinović-Runić, Jasmina and Djuran, Milos", year = "2019", abstract = "Five novel silver(I) complexes with 4,7-phenanthroline (4,7-phen), [Ag(NO3-O)(4,7-phen-mu-N4,N7)](n) (1), [Ag(ClO4-O)(4,7-phen-mu-N4,N7)](n) (2), [Ag(CF3COO-O)(4,7-phen-mu-N4,N7)](n) (3), [Ag-2(H2O)(0.58)(4,7-phen)(3)](SbF6)(2) (4) and {[Ag-2(H2O)(4,7-phen-mu-N4,N7)(2)](n)(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 mu M. 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.", publisher = "Elsevier Science Inc, New York", journal = "Journal of Inorganic Biochemistry", title = "Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection", pages = "163-149", volume = "195", doi = "10.1016/j.jinorgbio.2019.03.017" }
Pavić, A., Savić, N. D., Glišić, B., Crochet, A., Vojnović, S., Kurutos, A., Stanković, D., Fromm, K. M., Nikodinović-Runić, J.,& Djuran, M.. (2019). Silver(I) complexes with 4,7-phenanthroline efficient in rescuing the zebrafish embryos of lethal Candida albicans infection. in Journal of Inorganic Biochemistry Elsevier Science Inc, New York., 195, 149-163. https://doi.org/10.1016/j.jinorgbio.2019.03.017
Pavić A, Savić ND, Glišić B, Crochet A, Vojnović S, Kurutos A, Stanković D, Fromm KM, Nikodinović-Runić J, Djuran M. 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, Savić, Nada D., Glišić, Biljana, Crochet, Aurelien, Vojnović, Sandra, Kurutos, Atanas, Stanković, Dalibor, Fromm, Katharina M., Nikodinović-Runić, Jasmina, Djuran, Milos, "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 . .