The continuous increase in the incidence of infectious diseases and the rapid unchecked rise in multidrug-resistance to conventional antibiotics have led to the search for alternative strategies for treatment and clinical management of microbial infections. Since quorum sensing (QS) regulates numerous virulence determinants and pathogenicity in bacteria, inhibition of QS promises to be an attractive target for development of novel therapeutics. In this study, a series of cinnamic acid analogs and benzalacetone analogs were designed and synthesized, and their QS-inhibitory activities explored. We found that, among the test compounds, 4-methoxybenzalacetone (8) exhibited potent anti-quorum sensing property, as evidenced by inhibition of QS-controlled violacein production of Chromobacterium violaceum ATCC12472. The inhibitory activity of such a compound, which was the methyl keto analog of the corresponding cinnamic acid, was not only stronger than the parent cinnamic acid (1), but also superior to that of furanone, the reference drug. Based on our observations, its mechanism of quorum sensing inhibition is likely to be mediated by interference with N-acyl-homoserine lactones (AHL) synthesis. Moreover, 4-methoxybenzalacetone (8) also suppressed the production of pyocyanin, rhamnolipids and swarming motility of Pseudomonas aeruginosa, suggesting a broad spectrum of anti-QS activities of this compound. In terms of structure–activity relationship, the possible chemical substitutions on the scaffold of cinnamic acid required for QS inhibitory activity are also discussed. Since 4-methoxybenzalacetone (8) showed no toxicity to both bacteria and mammalian cells, our findings therefore indicate the anti-QS potential of this compound as a novel effective QS inhibitor.

传染病发病率的持续增加以及对传统抗生素的多重耐药性的迅速上升，导致人们寻找治疗和临床微生物感染的替代策略。由于群体感应 (QS) 调节细菌中的许多毒力决定因素和致病性，因此抑制 QS 有望成为开发新疗法的有吸引力的目标。在这项研究中，设计并合成了一系列肉桂酸类似物和苯扎丙酮类似物，并探索了它们的 QS 抑制活性。我们发现，在测试化合物中，4-甲氧基苯扎丙酮( 8 ) 表现出强大的反群体感应特性，这可以通过抑制紫色色杆菌的 QS 控制的紫罗兰素产生来证明。ATCC12472。这种化合物是相应肉桂酸的甲基酮类似物，其抑制活性不仅强于母体肉桂酸( 1 )，而且优于参比药物呋喃酮。根据我们的观察，其群体感应抑制机制可能是通过干扰 N-酰基高丝氨酸内酯 (AHL) 合成来介导的。此外，4-甲氧基苄基丙酮 ( 8 ) 还抑制绿脓杆菌的绿脓素、鼠李糖脂和蜂群运动的产生。，表明该化合物具有广谱的抗 QS 活性。在构效关系方面，还讨论了 QS 抑制活性所需的肉桂酸支架上可能的化学取代。由于 4-甲氧基苯扎丙酮 ( 8 ) 对细菌和哺乳动物细胞均无毒性，因此我们的研究结果表明该化合物作为新型有效 QS 抑制剂的抗 QS 潜力。