Park Suzie, Kim Han-Shin, Ok Kiwon, Kim YunHye, Park Hee-Deung, Byun Youngjoo
College of Pharmacy, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 339-700, South Korea.
School of Civil, Environmental and Architectural Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, South Korea.
Bioorg Med Chem Lett. 2015 Aug 1;25(15):2913-7. doi: 10.1016/j.bmcl.2015.05.054. Epub 2015 May 28.
Novel pyrone-derived quorum sensing (QS) ligands to inhibit the binding of OdDHL to the LasR of Pseudomonas aeruginosa were designed, synthesized and evaluated. Among the analogs, the most potent compound 8 exhibited strong in vitro inhibitory activities against biofilm formation and down-regulated OdDHL/LasR-associated genes by 35-67%. The binding mode of 8 in silico was highly similar to that of the crystal ligand OdDHL in the active site of LasR.
设计、合成并评估了新型吡喃酮衍生的群体感应（QS）配体，以抑制3-氧代十二烷酰高丝氨酸内酯（OdDHL）与铜绿假单胞菌LasR的结合。在这些类似物中，最有效的化合物8对生物膜形成表现出很强的体外抑制活性，并使与OdDHL/LasR相关的基因下调35%-67%。化合物8在计算机模拟中的结合模式与晶体配体OdDHL在LasR活性位点的结合模式高度相似。
