Novel hamamelitannin analogues for the treatment of biofilm related MRSA infections-A scaffold hopping approach.
Antimicrobial research is increasingly being focused on the problem of resistance and biofilm formation. Hamamelitannin (HAM) was recently identified as an antimicrobial potentiator for conventional antibiotics towards Staphylococcus aureus. This paper describes the synthesis and biological evaluation of novel hamamelitannin analogues with alternative central scaffolds. Via a ligand-based approach, several interesting compounds with improved synthetic accessibility were identified as potentiators for vancomycin in the treatment of MRSA infections.
Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Arno
A
Vermote
Laboratory for Pharmaceutical Microbiology, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Gilles
G
Brackman
Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Martijn D P
MDP
Risseeuw
Laboratory for Pharmaceutical Microbiology, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Tom
T
Coenye
Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: serge.vancalenbergh@ugent.be.
Serge
S
Van Calenbergh
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006601:Hexoses / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D014584:User-Computer Interface
D000900:Anti-Bacterial Agents; D006601:Hexoses; D008024:Ligands; D005707:Gallic Acid; C093412:hamamelitannin
Antibiotic potentiators; Hamamelitannin analogues; MRSA; Quorum sensing; Scaffold hopping