International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, College of Pharmacy, Jinan University, Guangzhou 510632; PR China; Faculty of Medicine and Health, the University of Sydney, Sydney, NSW 2006, Australia.
International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, College of Pharmacy, Jinan University, Guangzhou 510632; PR China.
Eur J Pharm Sci. 2019 Dec 1;140:105058. doi: 10.1016/j.ejps.2019.105058. Epub 2019 Aug 28.
The biofilm formation of Pseudomonas aeruginosa (P. aeruginosa) is regulated by a phenomenon of quorum sensing (QS). With 5-hydroxyl-3,4-halogenated-5H-furan-2-ones as beginning, analogs bearing alkyl chains, vinyl bromide, or aromatic rings were designed and synthesized. The minimum inhibitory concentration (MIC) of the compounds against P. aeruginosa was assayed and the biofilm inhibition ratio was determined at different concentrations lower than the MIC. C-5 aromatic substituted furanones showed remarkable biofilm formation as well as inhibition of virulence factor production in P. aeruginosa. Fluorescence report analysis identified the QS regulatory mechanism of the most active compound 29. This study provides us a novel candidate for combating drug resistant bacteria strains by merely inhibiting biofilm formation. Without suppressing the regular life cycle of the bacteria, bacterial resistance mechanisms may not be activated.
铜绿假单胞菌（P. aeruginosa）的生物膜形成受到群体感应（QS）现象的调节。以 5-羟基-3,4-卤代-5H-呋喃-2-酮为起始物，设计并合成了带有烷基链、溴乙烯基或芳环的类似物。测定了化合物对铜绿假单胞菌的最小抑菌浓度（MIC），并在低于 MIC 的不同浓度下测定了对生物膜的抑制率。C-5 取代的芳族呋喃酮显示出对铜绿假单胞菌生物膜形成以及毒力因子产生的显著抑制作用。荧光报告分析确定了最活跃化合物 29 的 QS 调节机制。这项研究为我们提供了一种通过抑制生物膜形成来对抗耐药菌的新候选药物。由于不抑制细菌的正常生命周期，细菌的耐药机制可能不会被激活。
