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

• Published in: International journal of molecular sciences 2024-08, Vol.25 (15), p.8023
• Main Authors: Ammanath, Aparna Viswanathan, Matsuo, Miki, Wang, Huanhuan, Kraus, Frank, Bleisch, Anton, Peslalz, Philipp, Mohammad, Majd, Deshmukh, Meghshree, Grießhammer, Anne, Purkayastha, Moushumi, Vorbach, Andreas, Macek, Boris, Brötz-Oesterhelt, Heike, Maier, Lisa, Kretschmer, Dorothee, Peschel, Andreas, Jin, Tao, Plietker, Bernd, Götz, Friedrich
• Format: Article
• Language: English
• Subjects: analogs & derivatives; Animals; Anti-Bacterial Agents; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial agents; Bacterial infections; chemistry; Clinical Medicine; Cytotoxicity; drug effects; drug therapy; Enterococcus faecium; Enterococcus faecium - drug effects; Gram-positive bacteria; Humans; Investigations; Ketones; Ketones - chemistry; Ketones - pharmacology; Klinisk medicin; Larva; Larva - drug effects; Ligands; Methicillin; Methicillin-Resistant Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus - drug effects; Mice; Microbial Sensitivity Tests; Molecular Docking Simulation; Moths; Moths - drug effects; Pathogens; pharmacology; Phloroglucinol; Proteins; Spiro Compounds; Spiro Compounds - chemistry; Spiro Compounds - pharmacology; Staphylococcal Infections; Staphylococcal Infections - drug therapy; Staphylococcus infections
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25158023

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 (MRSA) and vancomycin-resistant . Both compounds had no adverse effects on wax moth larvae. However, they were unable to protect the larvae from infection with 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 load in kidneys; in a mouse skin abscess model, topical treatment with PPAP53 reduced counts. Both PPAPs were active against anaerobic Gram-positive gut bacteria such as neurotransmitter-producing , or species. Based on these results, we foresee possible applications in the decolonization of pathogens.