4-Alkyliden-azetidinones modified with plant derived polyphenols: Antibacterial and antioxidant properties

Eur J Med Chem. 2017 Nov 10:140:604-614. doi: 10.1016/j.ejmech.2017.09.048. Epub 2017 Sep 23.

Abstract

Antimicrobial resistance is one of the major and growing concerns in hospital- and community acquired infections, and new antimicrobial agents are therefore urgently required. It was reported that oxidative stress could contribute to the selection of resistant bacterial strains, since reactive oxygen species (ROS) revealed to be an essential driving force. In the present work 4-alkylidene-azetidinones, a new class of antibacterial agents, were functionalized with phytochemical polyphenolic acids such as protocatechuic, piperonyl, caffeic, ferulic, or sinapic acids and investigated as dual target antibacterial-antioxidant compounds. The best candidates showed good activities against multidrug resistant clinical isolates of MRSA (MICs 2-8 μg/mL). Among the new compounds, two revealed the best antioxidant capacity with TEAC-DPPH and TEAC-ABTS being significantly more active than Trolox®.

Keywords: Antibacterials; Antioxidant capacity; Azetidinones; Gram-positive; Lactams; ROS; Resistant bacteria.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Azetidines / chemistry*
  • Azetidines / pharmacology
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Chromatography, High Pressure Liquid
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Microbial Sensitivity Tests
  • Polyphenols / chemistry*
  • Proton Magnetic Resonance Spectroscopy
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • 2-azetidinone
  • Anti-Bacterial Agents
  • Antioxidants
  • Azetidines
  • Polyphenols