AI Article Synopsis
- PQS acts as a quorum sensing regulator and iron chelator, influencing the expression of iron transport systems like pyoverdine and pyochelin.
- A range of 2-substituted 3-hydroxy-1,6-dimethylpyridin-4-ones was developed as potential biofilm inhibitors.
- One specific compound demonstrated 68.67% biofilm inhibition at 20 μM, targeting the QS systems and competing with pyoverdine for iron, leading to bacterial iron deficiency.
Article Abstract
2-Heptyl-3-hydroxy-4(1)-quinolone (PQS), a compound from , functions as both a quorum sensing (QS) regulator and a potent iron chelator to induce expression of pyoverdine and pyochelin which are involved in high-affinity iron transport systems. A potential dual-acting antibiofilm strategy requires molecules designed to interfere with iron uptake and the QS system of . A series of 2-substituted 3-hydroxy-1,6-dimethylpyridin-4-ones have been designed, synthesized, and tested as biofilm inhibitors of One compound, -((1,3,6-trimethyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)hexanamide (), exhibits 68.67% biofilm inhibitory activity at 20 μM. Further mechanistic studies have confirmed that this compound not only inhibits the QS systems of but also acts as an iron chelator to compete strongly with pyoverdine, causing iron deficiency in bacteria. The pyoverdine receptor FpvA was revealed as the target of by the mutant strain, -overexpressed strain, and studies.
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| http://dx.doi.org/10.1021/acs.jmedchem.0c00763 | DOI Listing |
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