The aim of the study was screening of chemical compounds library to find “quorum sensing” modulators in proteobacteria. The library included 19 molecules that contained the N-hexanamide non-polar radical or the 2H-1,3-benzodioxole polar heterocyclic group, which were partially identical to the natural autoinductor N-hexanoyl homoserine lactone (C6-AHL) chemical structure. The Chromobacterium violaceum CV026 (NCTC 13278) was used in “quorum sensing” modulation biotests. This biosensor strain is defective in the natural autoinducer C6-AHL biosynthesis, but contains the functional homodimeric protein CviR, which, after two C6-AHL molecules reception, activates the previously silent genes transcription, including the vioABCDE operon, which leads to the production of the blue-violet pigment violacein. The direct screening showed agonistic (violacein-inducing) activity in 4 compounds and the screening variant in presence of exogenously introduced C6-AHL indicated the antagonistic (violacein-inhibiting) activity in 9 tested compounds. Interestingly, the most pronounced antagonistic activity was found in molecules that proved to be C6-AHL agonists. Significantly, the effective concentrations of these compounds required for 50% violacein inhibition were 3.2–20.4-fold lower than ones causing 50% violacein induction. In addition, the absolute concentrations of the active compounds necessary for the induction of violacein were much higher than that of a natural autoinducer, and the degree of their inhibitory effect was inversely related to the concentration of C6-AHL exogenously introduced into the biotest. According to the screening results, N-1,3-benzodioxol-5-yl-oxohexanamide was identified as the most effective “quorum sensing” modulator, submitted for further in silico, in vitro and in vivo studies.

中文翻译：

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筛选 N-己酰胺和 2H-1,3-苯并二氧杂环己烷衍生物以调节紫色色杆菌中的群体感应

该研究的目的是筛选化合物库以在变形菌中找到“群体感应”调节剂。该库包括 19 个含有 N-己酰胺非极性基团或 2H-1,3-苯并二氧戊环极性杂环基团的分子，这些分子与天然自诱导剂 N-己酰基高丝氨酸内酯 (C6-AHL) 化学结构部分相同。紫色色杆菌 CV026 (NCTC 13278) 用于“群体感应”调节生物测试。这种生物传感器菌株在天然自诱导剂 C6-AHL 生物合成中存在缺陷，但包含功能性同源二聚体蛋白 CviR，在接收两个 C6-AHL 分子后，激活先前沉默的基因转录，包括 vioABCDE 操纵子，从而导致产生蓝紫色颜料紫罗兰素。直接筛选显示了 4 种化合物的激动（紫红素诱导）活性，并且在外源引入的 C6-AHL 存在下筛选变体表明 9 种测试化合物具有拮抗（紫红素抑制）活性。有趣的是，在被证明是 C6-AHL 激动剂的分子中发现了最显着的拮抗活性。值得注意的是，50% 紫罗兰素抑制所需的这些化合物的有效浓度比引起 50% 紫罗兰素诱导的化合物低 3.2-20.4 倍。此外，诱导紫罗兰素所需的活性化合物的绝对浓度远高于天然自诱导剂，其抑制作用的程度与外源性引入生物测试的 C6-AHL 浓度成反比。根据筛选结果，N-1，