Inhibition of beta-lactamase by 1,4-naphthalenedione from the plant Holoptelea integrifolia.
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.
Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Palayad P. O., Kannur, Kerala, 670661, India.
N V
NV
Vinod
R
R
Shijina
K V
KV
Dileep
C
C
Sadasivan
D000658:Amoxicillin / Q000494:pharmacology; D020134:Catalytic Domain; D057075:Enzyme Assays; D008401:Gas Chromatography-Mass Spectrometry; D006860:Hydrogen Bonding / Q000187:drug effects; D008024:Ligands; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013379:Substrate Specificity / Q000187:drug effects; D034401:Ulmaceae / Q000737:chemistry*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry
D008024:Ligands; D009285:Naphthoquinones; D065093:beta-Lactamase Inhibitors; D000658:Amoxicillin; D001618:beta-Lactamases; C035342:1,4-naphthoquinone