Design, synthesis and biological evaluation of 2-substituted 3-hydroxy-6-methyl-4H-pyran-4-one derivatives as Pseudomonas aeruginosa biofilm inhibitors

作者：Li, Yi-Bin; Liu, Jun; Huang, Zhi-Xing; Yu, Jia-Hui; Xu, Xiao-Fang; Sun, Ping-Hua; Lin, Jing^*; Chen, Wei-Min^*

来源：European Journal of Medicinal Chemistry, 2018, 158: 753-766.

DOI：10.1016/j.ejmech.2018.09.041

• Pseudomonas aeruginosa
• Quorum sensing
• PQS pathway
• Biofilm inhibitor
• Synthesis

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.

• 出版日期2018-10-5
• 单位暨南大学