Inhibition of beta-lactamase by 1,4-naphthalenedione from the plant Holoptelea integrifolia

Appl Biochem Biotechnol. 2010 Mar;160(6):1752-9. doi: 10.1007/s12010-009-8656-2. Epub 2009 May 9.

Abstract

The most important mechanism of the beta-lactam antibiotic resistance is the destruction of the antibiotics by the enzyme beta-lactamase. Use of beta-lactamase inhibitors in combination with antibiotics is one of the successful antibacterial strategies. The inhibitory effect of a phytochemical, 1,4-naphthalenedione, isolated from the plant Holoptelea integrifolia on beta-lactamase is reported here. This compound was found to have a synergistic effect with the antibiotic amoxicillin against a resistant strain of Staphylococcus aureus. The enzyme was purified from the organism and incubated with the compound. An assay showed that the compound can inhibit the enzymatic activity of beta-lactamase. Modeling and molecular docking studies indicated that the compound can fit into the active site of beta-lactamase. Hence, the compound can serve as a potential lead compound for the development of effective beta-lactamase inhibitor that can be used against beta-lactam-resistant microbial strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin / pharmacology
  • Catalytic Domain
  • Enzyme Assays
  • Gas Chromatography-Mass Spectrometry
  • Hydrogen Bonding / drug effects
  • Ligands
  • Naphthoquinones / chemistry
  • Naphthoquinones / isolation & purification*
  • Naphthoquinones / pharmacology*
  • Spectroscopy, Fourier Transform Infrared
  • Substrate Specificity / drug effects
  • Ulmaceae / chemistry*
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / chemistry

Substances

  • Ligands
  • Naphthoquinones
  • beta-Lactamase Inhibitors
  • Amoxicillin
  • beta-Lactamases
  • 1,4-naphthoquinone