Continuous Flow Synthesis and Antimicrobial Evaluation of NHC* Silver Carboxylate Derivatives of SBC3 in vitro and in vivo

Added on:
6 Jan, 2021

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 hypothesised virulence targeting substituents into NHC-silver systems via salt metathesis, an atom efficient complexation process can 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. pneumonia; further studies also confirmed the ability to inhibit biofilm formation in Methicillin-resistant S. aureus 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*).

  • Cillian O’Beirne†a
  • Magdalena E. Piatekb
  • Jen Fossenc
  • Helge Müller-Bunza
  • David R. Andesc
  • Kevin Kavanaghb
  • Siddappa A. Patild
  • Marcus Baumanna
  • Matthias Tacke†a
  • aSchool of Chemistry, University College Dublin, Belfield, Stillorgan, Dublin 4, Republic of Ireland
  • bSSPC Pharma Research Centre, Department of Biology, Maynooth University, Maynooth, W23F2H6, Co. Kildare, Republic of Ireland
  • cJ. Fossen, Prof. D. R. Andes, Department of Medicine, 600 Highland Avenue, University of Wisconsin, Madison, USA
  • dCentre for Nano and Material Sciences, Jain University, Bangalore, Karnataka, India
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