Molecular Docking Studies of Novel Furan-azetidinone Hybrids as Potential Inhibitors of Escherichia coli

Abstract:

Escherichia coli is the predominant gram negative bacteria responsible for a variety of hospital-acquired infections and urinary tract infections. As the bacterial strains are rapidly acquiring resistance to the available antibiotics, there is a need to discover novel antibacterial agents with different scaffolds. In this study, sixteen novel furan derivatives containing the azetidinone moiety were designed and synthesized to arrive at potentially effective antibacterial agents. In silico antibacterial activity was carried out to identify the specificity of the furan derivatives for the antibacterial targets. Molecular docking studies were conducted on four antibacterial targets of E. coli; Dihydrofolate reductase, DNA gyrase, Enoyl reductase and methionine aminopeptidase. Energy minimization of title compounds was carried out and they were docked on to the active site of the enzymes. Ligands were ranked according to their docking scores and their binding energy with the enzyme. The results obtained for the molecular docking of the title compounds with enoyl reductase of E. coli is quite promising. The study suggests that compounds 4E and 4D are potential inhibitors of enoyl reductase and specifically bind to the enzyme.

Key words: Furan, Azetidinone, E. coli, Docking, Anti-bacterial activity.