Investigation of a Series of Silver–N-Heterocyclic Carbenes as Antibacterial Agents: Activity, Synergistic Effects, and Cytotoxicity
✍ Scribed by Dr. Sylvain Roland; Dr. Claude Jolivalt; Dr. Thierry Cresteil; Laure Eloy; Pascale Bouhours; Arnaud Hequet; Dr. Virginie Mansuy; Dr. Corinne Vanucci; Prof. Jean-Marc Paris
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 228 KB
- Volume
- 17
- Category
- Article
- ISSN
- 0947-6539
No coin nor oath required. For personal study only.
✦ Synopsis
An impressive amount of research has been dedicated to the preparation of metal N-heterocyclic carbene (NHC) complexes and to the development of catalytic applications. [1] By comparison, biological applications of metal-NHCs have been much less explored. Various studies focusing on the antimicrobial or anticancer activity have highlighted their promising potential as novel therapeutic agents. [2] Metal-NHCs (metal = Ru, Rh, Au, or Ag) have been investigated for their antimicrobial activity against a number of bacterial and fungal strains. [3] Some of these complexes, such as 1-7 (Scheme 1), showed significant activities against Gram-negative and/or Gram-positive bacteria with minimum inhibitory concentrations (MICs) below 10 mg mL À1 , [2a, 4] which is a minimal value generally recognized in the pharmaceutical industry for a valuable hit to be further developed as a potential drug. In recent decades, with the growing appearance of multidrug-resistant (MDR) bacterial strains, [5] silver has reemerged as a viable and useful antibacterial agent. At present, silver-based compounds are commonly used in the topical chemotherapy of infections encountered in burns, open wounds, and chronic ulcers. [6] Silver, as silver salt (AgNO 3 ), nanocrystalline silver (silver-coated dressings), or in combination with antibiotics (silver sulfadiazine), has been incorporated into several commercial products. However, the development of new and more efficient silver-based antibacterial drugs is still of interest. One of the main challenges is to improve the ability to provide sustained bactericidal action while lowering the toxicity. [6, 7] In this context, stable silver-NHCs have given promising results. [3d-l] Some of these, such as 6 and 7 (Scheme 1), have been found to exhibit high in vitro antimicrobial efficacy against a broad spectrum of highly resistant respiratory pathogens and against E. coli with MIC values as low as 1 mg mL À1 . [3g-i] Silver-NHCs have also been shown to be active against S. aureus. [3d, f, i] However, the potential against resistant strains of S. aureus, which cause major problems to public health due to MDR strains in hospitals and community infections, [5] has only been scarcely investigated. A few complexes, including 6, have been reported to be effective against methicillin-resistant S. aureus (MRSA). [3i] The implications of in vitro cytotoxicity of silver for clinical wound care has been well studied. [7] Currently, little information is available on the cytotoxic effects of silver-NHCs tested as antimicrobial agents. One noteworthy ex-[a] Dr.