Abstract

Background: Escherichia coli especially its multiresistant strains as the common foodborne pathogens cause bloodstream 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 a series of imidazolium-based Ionic Liquids (ILs) against E. coli spp.

Methods: M2D fragment-based, classification and regression QSAR models were created using machine learning methods and types of descriptors via the OCHEM server. Biological testing of a series of synthesized imidazolium ILs with predicted activity was performed by the 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 Enoyl-Acyl 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 a 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 is 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.

Keywords: Imidazolium ionic liquids, QSAR modeling, antibacterial activity, Escherichia coli, molecular docking, enoyl-acyl carrier protein reductase.

Graphical Abstract