当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > 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).

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).

Abstract：

: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.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Sovari SN,Vojnovic S,Bogojevic SS,Crochet A,Pavic A,Nikodinovic-Runic J,Zobi F

doi

10.1016/j.ejmech.2020.112533

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

112533

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(20)30505-5

journal_volume

205

pub_type

杂志文章

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