Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 158, Issue -, Pages 753-766Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.09.041
Keywords
Pseudomonas aeruginosa; Quorum sensing; PQS pathway; Biofilm inhibitor; Synthesis
Categories
Funding
- National Natural Science Foundation of China [81673336]
- Pearl River S&T Nova Program of Guangzhou [201806010116]
- Fundamental Research Funds for the Central University [21617478]
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Drug-resistant bacteria associated with biofilm formation are rapidly on the rise, requiring novel therapeutic options to combat biofilm induced drug-resistance. In this study, a class of 3-hydroxy-2-(phenylhydroxy-methyl)-6-methyl-4H-pyran-4-one derivatives (1a-le) were found by screening of an in-house compound library to be potential Pseudomonas aeruginosa biofilm inhibitors. Thirty one novel 2-substituted 3-hydroxy-6-methyl-4H-pyran-4-one derivatives were synthesized and assayed for their biofilm inhibitory activity. A promising biofilm inhibitor 6a was identified, and showed an obvious biofilm inhibitory effect even at a concentration of 2.5 mu M. Further mechanism studies revealed that 6a only shows inhibitory effects on the expression of pqsA-gfp in a fluorescent reporter strain, and the production of a PQS- regulated virulence factor, pyocyanin. This indicates that this type of compound exercises its anti-biofilm activity specifically through the PQS pathway. Novel chemical biofilm inhibitors are described here and guard against biofilm formation associated with Pseudomonas aeruginosa infections. (C) 2018 Elsevier Masson SAS. All rights reserved.
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