Antimicrobial Evaluation of Two Polycyclic Polyprenylated Acylphloroglucinol Compounds: PPAP23 and PPAP53

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Aparna Viswanathan Ammanath - (Author)
  • Miki Matsuo - (Author)
  • Huanhuan Wang - (Author)
  • Frank Kraus - (Author)
  • Anton Bleisch - , Chair of Organic Chemistry I (Author)
  • Philipp Peslalz - , Chair of Organic Chemistry I (Author)
  • Majd Mohammad - (Author)
  • Meghshree Deshmukh - (Author)
  • Anne Grießhammer - (Author)
  • Moushumi Purkayastha - (Author)
  • Andreas Vorbach - (Author)
  • Boris Macek - (Author)
  • Heike Brötz-Oesterhelt - (Author)
  • Lisa Maier - (Author)
  • Dorothee Kretschmer - (Author)
  • Andreas Peschel - (Author)
  • Tao Jin - (Author)
  • Bernd Plietker - , Chair of Organic Chemistry I (Author)
  • Friedrich Götz - (Author)

Abstract

Polycyclic polyprenylated acylphloroglucinols (PPAPs) comprise a large group of compounds of mostly plant origin. The best-known compound is hyperforin from St. John’s wort with its antidepressant, antitumor and antimicrobial properties. The chemical synthesis of PPAP variants allows the generation of compounds with improved activity and compatibility. Here, we studied the antimicrobial activity of two synthetic PPAP-derivatives, the water-insoluble PPAP23 and the water-soluble sodium salt PPAP53. In vitro, both compounds exhibited good activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Both compounds had no adverse effects on Galleria mellonella wax moth larvae. However, they were unable to protect the larvae from infection with S. aureus because components of the larval coelom neutralized the antimicrobial activity; a similar effect was also seen with serum albumin. In silico docking studies with PPAP53 revealed that it binds to the F1 pocket of human serum albumin with a binding energy of −7.5 kcal/mol. In an infection model of septic arthritis, PPAP23 decreased the formation of abscesses and S. aureus load in kidneys; in a mouse skin abscess model, topical treatment with PPAP53 reduced S. aureus counts. Both PPAPs were active against anaerobic Gram-positive gut bacteria such as neurotransmitter-producing Clostridium, Enterococcus or Ruminococcus species. Based on these results, we foresee possible applications in the decolonization of pathogens.

Details

Original languageEnglish
Article number8023
JournalInternational journal of molecular sciences
Volume25
Issue number15
Publication statusPublished - Jul 2024
Peer-reviewedYes

External IDs

Scopus 85201009416
PubMed 39125595

Keywords