Molecular Docking and Antibacterial Assessment of Monocyclic β‐Lactams against Broad‐Spectrum and Nosocomial Multidrug‐Resistant Pathogens

Abstract

Abstractβ‐Lactam antibiotics are critical antibacterial agents and have rapidly become active ingredients in modern medicine. On the other hand, in the face of increasing rate of antibacterial resistance, there are many concerns requiring the design and synthesis of new antibacterial agents. Herein, we synthesized some monocyclic β‐lactams with various substituents through the Staudinger cycloaddition reaction. The formation of cycloadducts was confirmed by elemental analysis and different spectral data, including NMR, FTIR, and Mass spectroscopy. The investigation of in vitro antibacterial activity of synthesized β‐lactams was performed against some broad‐spectrum strains, including Escherichia coli (E. coli), streptococcus aureus (S. aureus), Salmonella Typhi (S. Typhi), Enterococcus faecalis (E. faecalis), and Candida albicans (C. albicans) and also some nosocomial multidrug‐resistant pathogens such as methicillin‐resistant Staphylococcus aureus (MRSA), and vancomycin‐resistant enterococci (VRE). Penicillin Binding Proteins (PBPs) are responsible for the cell wall synthesis process as an enzymatic target for β‐lactam antibiotics. The molecular docking study exhibited a good correlation between the calculated binding affinity to PBP and the experimental data. Based on the obtained results, compound 4 d was successfully fitted in the BPB active site, and could potentially serve as a promising lead compound for the treatment of infectious diseases.