Design, synthesis and biological evaluation of 2-substituted 3-hydroxy-6-methyl-4H-pyran-4-one derivatives as Pseudomonas aeruginosa biofilm inhibitors
| Autor: | Yi-Bin Li, Xiao-Fang Xu, Wei-Min Chen, Jia-Hui Yu, Ping-Hua Sun, Zhi-Xing Huang, Jing Lin, Jun Liu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
030106 microbiology medicine.disease_cause Methylation Virulence factor Microbiology Mice 03 medical and health sciences chemistry.chemical_compound Pyocyanin Drug Discovery medicine Animals Humans Pseudomonas Infections Pyrans Pharmacology Strain (chemistry) biology Pseudomonas aeruginosa Organic Chemistry Biofilm Quorum Sensing General Medicine biochemical phenomena metabolism and nutrition biology.organism_classification Anti-Bacterial Agents Quorum sensing RAW 264.7 Cells chemistry Pyran Biofilms Bacteria |
| Zdroj: | European Journal of Medicinal Chemistry. 158:753-766 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2018.09.041 |
| Popis: | 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-1e) 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 μM. 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. |
| Databáze: | OpenAIRE |
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