1. Design, synthesis and biological evaluation of 2-substituted 3-hydroxy-6-methyl-4H-pyran-4-one derivatives as Pseudomonas aeruginosa biofilm inhibitors.
- Author
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Li, Yi-Bin, Liu, Jun, Huang, Zhi-Xing, Yu, Jia-Hui, Xu, Xiao-Fang, Sun, Ping-Hua, Lin, Jing, and Chen, Wei-Min
- Subjects
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PYRANONES , *PSEUDOMONAS aeruginosa , *BIOFILMS , *CHEMICAL derivatives , *DRUG design , *ORGANIC synthesis , *DRUG resistance in bacteria - Abstract
Abstract 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-4 H -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-4 H -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. Graphical abstract Image 1 Highlights • Four series of 2-substituted 3-hydroxy-6-methyl-4 H -pyran-4-one derivatives were synthesized. • Potent biofilm inhibitor 6a exhibited excellent Pseudomonas aeruginosa biofilm inhibitory effect were identified. • The PQS pathway specific anti-biofilm mechanism of this type of compound was uncovered. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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