ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Manuscript_Nasiri et al_FZ_ESI.pdf (4.55 MB)
0/0

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)

preprint
submitted on 21.04.2020 and posted on 23.04.2020 by Sara Nasiri Sovari, Sandra Vojnovic, Sanja Skaro Bogojevic, Aurélien Crochet, Aleksandar Pavic, Jasmina Nikodinovic-Runic, Fabio Zobi

Preparation of a series of ten 3-arylcoumarin molecules, their respective fac-[Re(CO)3(bpy)L]+ and fac-[Re(CO)3(L⁀L)Br] complexes. All compounds were tested 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.

Funding

University of Fribourg

Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant No. 173048)

History

Email Address of Submitting Author

fabio.zobi@unifr.ch

Institution

Université de Fribourg

Country

Switzerland

ORCID For Submitting Author

0000-0002-9077-7184

Declaration of Conflict of Interest

No conflict of interest

Exports