Novel N-benzoylimidazolium ionic liquids derived from benzoic and hydroxybenzoic acids as therapeutic alternative against Biofilm-forming bacteria in skin and soft-tissue infections.

The skin and soft tissue infections (SSTIs) -producing pathogens have acquired resistance to a wide range of antimicrobials, thus it is highly relevant to have new treatment alternatives. In this study, we report the synthesis, characterization, and antibacterial activity of three novel series of ionic liquids (ILs) derived from benzoic and hydroxybenzoic acids, with different lengths of the alkyl chain. The minimum inhibitory concentration (MIC) were tested in Gram-positive: Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes, and Gram-negative: Acinetobacter baumannii and Escherichia coli, showing a MIC range of 0.01562-2.0 mM, with the activity varying according to the aromatic ring functionalization and the length of the alkyl chains. Regarding the antibiofilm activity, different efficacy was observed among the different ILs, some of them presenting antibiofilm activities close to 80% as in the case of those derived from syringic acid with an alkyl chain of six carbon atoms against Pseudomonas aeruginosa. Furthermore, the cell viability in HaCaT cells was determined, showing a half maximal effective concentration (EC50) values higher than the MIC values. The antimicrobial and antibiofilm results, along with not producing cellular toxicity at the MIC values shows that these ILs could be a promising alternative against SSTIs.

Antimicrobial properties of novel ionic liquids derived from imidazolium cation with phenolic functional groups.

Bacterial infections are nowadays among the major threats to public health worldwide. Thus, there is an urgent and increased need for new antimicrobial agents. As a result, the exploration of the antimicrobial properties of different substances including ionic liquids (ILs) has recently attracted great attention. The present work is aimed at evaluating how the addition of halogens and hydrophobic substituents on alkylimidazolium units of ILs as well as the increase in their chain lengths affects the antimicrobial properties of such ILs. After their synthesis, the antibacterial activities of these compounds against Pseudomona aeruginosa, Escherichia coli, and Staphylococcus aureus are determined by measuring their minimal inhibitory concentrations (MICs). Key features in ILs-membrane interactions are also studied using long-term all-atom molecular dynamics simulations (MDs). The results show that these ILs have good antibacterial activity against S. aureus, E. coli, and P. aeruginosa, with MIC values range from <7.81 to 62.50 µM. The antimicrobial property of tert-butyl N-methylphenolimidazolium salts (denoted as 8b and 8c) is particularly better with MIC values of < 7.81 µM. The antibacterial efficacy is also found to depend on the alkyl chain length and substituents on the phenolic ring. Finally, MDs done for ILs in a phosphatidylcholine (POPC) bilayer show key features in the mechanism of IL-induced membrane disruption, where the ILs are inserted as clusters into one side of the bilayer until saturation is reached. This insertion increases "leaflet strain" up to critical threshold, likely triggering the morphological disruption of the membranes in the microbes.