College of Pharmaceutical Science & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, P. R. China.
Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University & Anhui Center for Surveillance of Bacterial Resistance, Hefei, P. R. China.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2175820. doi: 10.1080/14756366.2023.2175820.
Six series of benzoheterocyclic sulfoxide derivatives were designed and synthesised as () quorum sensing inhibitors in this paper. We experimentally demonstrated that significantly inhibited the formation of PAO1 biofilm without affecting the growth. Further mechanistic studies showed that affected the luminescence of quorum sensing reported strain PAO1-- and the production of PAO1 elastase virulence factor which was regulated by system. These experimental results indicate that acts as a quorum sensing inhibitor mainly through the system. Furthermore, silico molecular docking studies demonstrated that and the quorum sensing receptor LasR were molecularly bound via hydrogen bonding interactions. Preliminary structure-activity relationship and docking studies illustrated that shows great promise as anti-biofilm compounds for further studies in order to solve the problem of microbial resistance in future.
本文设计并合成了六组苯并杂环亚砜衍生物作为（）群体感应抑制剂。实验表明，该化合物在不影响生长的情况下，显著抑制了 PAO1 生物膜的形成。进一步的机制研究表明，该化合物通过影响群体感应报告菌株 PAO1--的发光和由群体感应系统调节的 PAO1 弹性蛋白酶毒力因子的产生来发挥作用。这些实验结果表明，该化合物主要通过群体感应系统发挥作用。此外，通过计算机分子对接研究表明，该化合物与群体感应受体 LasR 通过氢键相互作用结合。初步的构效关系和对接研究表明，该化合物具有很大的作为抗生物膜化合物的潜力，以便进一步研究，以解决未来微生物耐药性的问题。
