In an attempt to counteract bacterial pathogenicity, a set of novel imidazolidine‐2,4‐dione and 2‐thioxoimidazolidin‐4‐one derivatives was synthesized and evaluated as inhibitors of bacterial virulence. The new compounds were characterized and screened for their effects on the expression of virulence factors of Pseudomonas aeruginosa, including protease, hemolysin, and pyocyanin. Imidazolidine‐2,4‐diones 4c, 4j, and 12a showed complete inhibition of the protease enzyme, and they almost completely inhibited the production of hemolysin at 1/4 MIC (1/4 minimum inhibitory concentration; 1, 0.5, and 0.5 mg/ml, respectively). 2‐Thioxoimidazolidin‐4‐one derivative 7a exhibited the best inhibitory activity (96.4%) against pyocyanin production at 1 mg/ml (1/4 MIC). A docking study was preformed to explore the potential binding interactions with quorum‐sensing receptors (LasR and RhlR), which are responsible for the expression of virulence genes.

中文翻译：

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作为铜绿假单胞菌毒力因子产生抑制剂的咪唑烷-2,4-二酮和2-硫代咪唑烷-4-酮衍生物的合成

为了对抗细菌致病性，合成了一组新型咪唑烷-2,4-二酮和 2-硫代咪唑烷-4-one 衍生物，并将其作为细菌毒力的抑制剂进行评估。对新化合物进行了表征并筛选了它们对铜绿假单胞菌毒力因子（包括蛋白酶、溶血素和绿脓素）表达的影响。咪唑烷-2,4-二酮 4c、4j 和 12a 显示出对蛋白酶的完全抑制，并且它们在 1/4 MIC（1/4 最小抑制浓度；1、0.5 和 0.5 mg）下几乎完全抑制了溶血素的产生/ml，分别）。2-Thiooxoimidazolidin-4-one 衍生物 7a 在 1 mg/ml (1/4 MIC) 时对绿脓菌素的产生表现出最好的抑制活性 (96.4%)。