Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. published the artcile< Discovery and biophysical characterization of 2-amino-oxadiazoles as novel antagonists of PqsR, an important regulator of Pseudomonas aeruginosa virulence>, COA of Formula: C8H6ClN3S, the main research area is aminooxadiazole antibacterial protein PqsR Pseudomonas.
The human pathogen Pseudomonas aeruginosa employs alkyl quinolones for cell-to-cell communication. The Pseudomonas quinolone signal (PQS) regulates various virulence factors via interaction with the transcriptional regulator PqsR. Therefore, the authors considered the development of PqsR antagonists as a novel strategy to limit the pathogenicity of P. aeruginosa. A fragment identification approach using surface plasmon resonance screening led to the discovery of chem. diverse PqsR ligands. The optimization of the most promising hit (5) resulted in the oxadiazole-2-amine 37 showing pure antagonistic activity in Escherichia coli (EC50 = 7.5 μM) and P. aeruginosa (EC50 = 38.5 μM) reporter gene assays. Compound 37 was able to diminish the production of the PQS precursor HHQ in a PqsH-deficient P. aeruginosa mutant. The level of the major virulence factor pyocyanin was significantly reduced in wild-type P. aeruginosa. In addition, site-directed mutagenesis in combination with isothermal titration calorimetry and NMR INPHARMA experiments revealed that the identified ligands bind to the same site of PqsR by adopting different binding modes. These findings might be utilized in a future fragment-growing approach aiming at novel therapeutic options for the treatment of P. aeruginosa infections.
Journal of Medicinal Chemistry published new progress about Antibacterial agents. 70057-67-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H6ClN3S, COA of Formula: C8H6ClN3S.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics