Abstract
The combination of the dehydroabietic acid scaffold with different amino acids resulted in the discovery of a new class of hybrid compounds that targets both planktonic and biofilms bacteria in Staphylococcus aureus strains and are far more potent anti-biofilm agents than conventional antibiotics. Unlike dehydroabietic acid, these compounds can disrupt biofilms within a short time period and compromise the integrity of the bacterial membrane. Two of the compounds identified in our study are the most potent abietane-type anti-biofilm agents reported so far and display robust activity against pre-formed biofilms at concentrations only 3-6-fold higher than those required to inhibit biofilm formation. Their easy preparation based on proteolysis-resistant d- and unusual amino acids makes them useful chemical probes to gain a deeper understanding of bacterial biofilms and outstanding candidates for further development into new drugs to fight infections.
Original language | English |
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Pages (from-to) | 68-79 |
Number of pages | 12 |
Journal | European Journal of Medicinal Chemistry |
Volume | 102 |
DOIs | |
Publication status | Published - 18 Sept 2015 |
Keywords
- anti-bacterial agents
- biofilms
- cell membrane
- Diterpenes, Abietane
- dose-response relationship, drug
- microbial sensitivity tests
- plankton
- Staphylococcus aureus
- structure-activity relationship