A New Class of Broad Spectrum Antimicrobial Agents

Diphosphonium ionic liquids may be a new class of broad spectrum antimicrobial agents, useful in fighting resistant bacterial pathogens in medicine.

There has been a recent trend in the increase of resistant strains of bacterial and fungal pathogens with a dearth of new antimicrobial agents. In particular, there is a need for antimicrobial agents for use on the ocular surface. It is difficult to treat ocular infections because compounds need to be safe for use on the ocular surface.  The US has relied primarily on topical fluoroquinolones since the early 1990s, but many bacterial strains are becoming resistant to these compounds.

George O’Toole et al. recently published a paper in Cornea identifying a class of compounds known as dicationic bisphonium ionic liquids that demonstrate antimicrobial activity against gram-positive and gram-negative strains of bacteria. Ionic liquids have primarily been used for industrial purposes, but it has been shown that monophosphonium ionic liquids are cytotoxic to both bacteria and corneal epithelial cells, suggesting a potential application in medicine. Dicationic bisphonium ionic liquids were synthesized and tested for their antimicrobial activity against laboratory and clinical strains of important eye pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa.

To determine the antimicrobial activity of these agents, the researchers measured the minimum bactericidal concentration, or the lowest concentration of the antibiotic needed to obtain complete loss of bacterial viability. Of the seven compounds they tested, one of the compounds, Di-Hex C10, showed the most robust antimicrobial activity. In vitro cytotoxicity assays were done using human corneal limbal epithelial cells, and it was shown that diphosphonium ionic liquids are not cytotoxic to corneal epithelial cells. In vivo studies using mice showed that Di-Hex C10 was not cytotoxic to mouse corneas.

Assays using these seven synthesized dicationic bisphonium ionic liquids showed that their activity varies with structure. In the future, structure-activity relationships studies and extensive animal testing will be important in determining the clinical potential of these compounds. Furthermore, future research will be done to determine the mechanism of action of these compounds. These compounds are promising in their antimicrobial activity, but the safety and in vivo efficacy must be established before clinical use.

References:

1. G. O’Toole et al., Cornea 0, 1-7 (2011).