In silico and in vitro studies of Imidazolium ionic liquids as effective antibacterial agents against multidrug resistant Escherichia coli strains

Background: Escherichia coli especially its multiresistant strains as the common foodborne pathogens cause blood stream infections, nosocomial pneumonia, infections of the skin and soft tissues. Therefore, the search for new effective biologically active compounds has been rapidly increasing in recent few decades. In this paper, we describe Quantitative Structure-Activity Relationships (QSAR) studies, molecular docking and in vitro antibacterial activity evaluation of series imidazolium-based ionic liquids (ILs) against E. coli spp. Methods: 2D fragment-based, classification and regression QSAR models were created using machine learning methods and types of descriptors via the OCHEM server. Biological testing of series of synthesized imidazolium ILs with predicted activity was performed by disc diffusion method. The most typical structures of symmetric and asymmetric ILs with high anti-E.coli activity (1e, 1h) were docked into the active site of enoylacyl carrier protein reductase (ENR) in E. coli. Results: Symmetric imidazolium ILs with C8 alkyl chain length demonstrated the highest antibacterial activity in comparison to the high antibacterial potential of asymmetric ILs with C12 alkyl chain length against drug-sensitive and drug-resistant E. coli strains including hemolytic E. coli. It should be noted that symmetric ILs with C6 or C9 alkyl chain length have the slightly lower activity against certain E. coli strains. The key role in the binding of compounds (1e, 1h) in the E. coli ENR active site associated with the NAD molecule and the amino acid residue Tyr146. Conclusion: The highly active symmetric and asymmetric imidazolium ILs can be considered as promising drug-candidates effective against E. coli spp. pathogens including multidrug resistant strains.