title: Synthesis and anti-biofilm activities of dihydro-pyrrol-2-one derivatives on Pseudomonas aeruginosa.
abstract: Biofilm formation is an important reason for bacterial resistance to antimicrobials. Many compounds with dihydro-pyrrol-2-one (DPO) have antibacterial effects. It is prospective to base on DPO skeleton to design new compounds for biofilm inhibition. DPO was designed by a novel method of tandem cyclization between ethyl glyoxalate and amines, the series of DPO derivatives were synthesized by change of the amines. Their activities were evaluated by the inhibition of biofilm in Pseudomonas aeruginosa. The interaction of DPO derivatives with mannitol dehydrogenase (MDH) or extracellular DNA (eDNA) in the biofilm was simulated by molecular docking to reveal possible mechanism. 19 new DPO derivatives were synthesized and identified, 15 of them had antibacterial activities, but only 5 of them had more than 50% inhibition on biofilm of P. aeruginosa at 50μg/mL. The MDH activity and eDNA content in biofilm decreased significantly after treatment of the DPO derivatives in concentration dependence. The simulation reveals that strong interaction exists between the five DPO derivatives and MDH or eDNA, which are involved in anti-biofilm mechanism. The synthetic method of DPO derivatives is practical to provide effective anti-biofilm agents for P. aeruginosa, and they take effect through inhibition on MDH and eDNA of biofilm.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China. Electronic address: yeyong@scut.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001665:Binding Sites; D018441:Biofilms / Q000187:drug effects*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D008354:Mannitol Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011758:Pyrroles; D004247:DNA; D008354:Mannitol Dehydrogenases
keywords: Bacterial biofilm; DPO derivatives; Extracellular DNA; Mannitol dehydrogenase; Tandem reaction