Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA)
- Sovari, Sara Nasiri University of Fribourg
- Vojnovic, Sandra University of Belgrade
- Bogojevic, Sanja Skaro University of Belgrade
- Crochet, Aurélien University of Fribourg
- Pavic, Aleksandar University of Belgrade
- Nikodinovic-Runic, Jasmina University of Belgrade
- Zobi, Fabio University of Fribourg
-
01.11.2020
Published in:
- European Journal of Medicinal Chemistry. - 2020, vol. 205, p. 112533
English
We have prepared a series of ten 3-arylcoumarin molecules, their respective fac- [Re(CO)3(bpy)L]+ and fac-[Re(CO)3(L⁀L)Br] complexes and tested all compounds for their antimicrobial efficacy. Whereas the 3-arylcoumarin ligands are virtually inactive against the human-associated pathogens with minimum inhibitory concentrations (MICs) > 150 μM, when coordinated to the fac-[Re(CO)3]+ core, most of the resulting complexes showed remarkable antibacterial potency. Several rhenium complexes exhibit activity in nanomolar concentrations against Gram-positive pathogens such as Staphylococcus aureus strains, including methicillin-resistant S. aureus (MRSA) and Enterococcus faecium. The molecules do not affect bacterial cell membrane potential, but some of the most potent complexes strongly interact with DNA, indicating it as a possible target for their mode of action. In vivo studies in the zebrafish model showed that the complexes with anti-staphylococcal/MRSA activity were non-toxic to the organism even at much higher doses of the corresponding MICs. In the zebrafish-MRSA infection model, the complexes increased the survival rate of infected fish up to 100% and markedly reduced bacterial burden. Moreover, all rescued fish developed normally following the treatments with the metallic compounds.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Chimie
- Language
-
- English
- Classification
- Chemistry
- License
- License undefined
- Identifiers
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- RERO DOC 329082
- DOI 10.1016/j.ejmech.2020.112533
- Persistent URL
- https://folia.unifr.ch/unifr/documents/308825
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