Helmholtz-Institute for Pharmaceutical Research Saarland, Campus C23, 66123 Saarbrücken, Germany.
J Am Chem Soc. 2012 Oct 3;134(39):16143-6. doi: 10.1021/ja3072397. Epub 2012 Sep 24.
2-Heptyl-4-hydroxyquinoline (HHQ) and Pseudomonas quinolone signal (PQS) are involved in the regulation of virulence factor production and biofilm formation in Pseudomonas aeruginosa. PqsD is a key enzyme in the biosynthesis of these signal molecules. Using a ligand-based approach, we have identified the first class of PqsD inhibitors. Simplification and rigidization led to fragments with high ligand efficiencies. These small molecules repress HHQ and PQS production and biofilm formation in P. aeruginosa. This validates PqsD as a target for the development of anti-infectives.
2-庚基-4-羟基喹啉（HHQ）和假单胞菌喹诺酮信号（PQS）参与铜绿假单胞菌毒力因子产生和生物膜形成的调节。PqsD 是这些信号分子生物合成的关键酶。我们采用基于配体的方法，鉴定了第一类 PqsD 抑制剂。简化和刚性化导致具有高配体效率的片段。这些小分子抑制铜绿假单胞菌中 HHQ 和 PQS 的产生和生物膜形成。这验证了 PqsD 是开发抗感染药物的靶标。
