Modified tetra-oxygenated xanthones analogues as anti-MRSA and P. aeruginosa agent and their synergism with vancomycin

Bioorg Med Chem Lett. 2020 Oct 15;30(20):127494. doi: 10.1016/j.bmcl.2020.127494. Epub 2020 Aug 12.

Abstract

Five isolated xanthones from the C. cochinchinense and G. mangostana were evaluated and tested for antibacterial activities. Isolated 4 and 5 exhibited potent anti-MRSA and P. aeruginosa activity, but showed poor pharmacokinetic properties via ADMET prediction. It led us to improve pharmacokinetic properties of 4 and 5 by partially modifying them in acidic condition yielding fourteen analogues. It was found that analogues 4b, 4d and 5b possessed proper pharmacokinetic properties, while only 4b exhibited the best anti-MRSA and P. aeruginosa activity. The SEM results indicated that 4b may interact with or damage the cell wall of MRSA and P. aeruginosa. Moreover, a combination of 4b and vancomycin exhibits synergistic effect against both MRSA and P. aeruginosa at MIC value of 4.98 (MIC = 18.75 μg/mL for 4b) and 9.52 μg/mL (MIC = 75 μg/mL for 4b), respectively.

Keywords: MRSA; P. aeruginosa; Synergism and ADMET; Vancomycin; Xanthone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Clusiaceae / chemistry
  • Dose-Response Relationship, Drug
  • Garcinia mangostana / chemistry
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects*
  • Structure-Activity Relationship
  • Vancomycin / chemistry
  • Vancomycin / pharmacology*
  • Xanthones / chemistry
  • Xanthones / isolation & purification
  • Xanthones / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Xanthones
  • Vancomycin