O'Beirne, Cillian and Piatek, Magdalena E and Fossen, Jen and Müller-Bunz, Helge and Andes, David R and Kavanagh, Kevin and Patil, Siddappa A and Baumann, Marcus and Tacke, Matthias (2020) Continuous flow synthesis and antimicrobial evaluation of NHC* silver carboxylate derivatives of SBC3 in vitro and in vivo. Metallomics, 13 (2). ISSN 1756-591X

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Abstract

N-heterocyclic silver carbene compounds have been extensively studied and shown to be active agents against a host of pathogenic bacteria and fungi. By incorporating hypothesized virulence targeting substituents into NHC–silver systems via salt metathesis, an atom-efficient complexation process can be used to develop new complexes to target the passive and active systems of a microbial cell. The incorporation of fatty acids and an FtsZ inhibitor have been achieved, and creation of both the intermediate salt and subsequent silver complex has been streamlined into a continuous flow process. Biological evaluation was conducted with in vitro toxicology assays showing these novel complexes had excellent inhibition against Gram-negative strains E. coli, P. aeruginosa, and K. pneumoniae; further studies also confirmed the ability to inhibit biofilm formation in methicillin-resistant Staphylococcus aureus (MRSA) and C. Parapsilosis. In vivo testing using a murine thigh infection model showed promising inhibition of MRSA for the lead compound SBC3, which is derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*

Item Type:	Article
Additional Information:	Cite as: O'Beirne, C., Piatek, M.E., Fossen, J., Müller-Bunz, H., Andes, D.R., Kavanagh, K., Patil, S.A., Baumann, M. & Tacke, M. 2021, "Continuous flow synthesis and antimicrobial evaluation of NHC silver carboxylate derivatives of SBC3 in vitro and in vivo", Metallomics, vol. 13, no. 2
Keywords:	antimicrobial agents; in vitro; SBC3;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17301
Identification Number:	https://doi.org/10.1093/mtomcs/mfaa011
Depositing User:	Dr. Kevin Kavanagh
Date Deposited:	08 Jun 2023 14:52
Journal or Publication Title:	Metallomics
Publisher:	Oxford
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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