Title:In silico and in vitro Studies of Imidazolium Ionic Liquids as Effective Antibacterial Agents against Multidrug Resistant Escherichia coli Strains
Volume: 17
Issue: 2
Author(s): Diana Hodyna*, Vasyl Kovalishyn, Ivan Semenyuta, Volodymyr Blagodatny, Sergiy Rogalsky and Larysa Metelytsia
Affiliation:
- Department of Medical and Biological Researches, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, Kyiv-94, 02094,Ukraine
Keywords:
Imidazolium ionic liquids, QSAR modeling, antibacterial activity, Escherichia coli, molecular docking, enoyl-acyl
carrier protein reductase.
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.
