Thioether-linked dihydropyrrol-2-one analogues as PqsR antagonists against antibiotic resistant Pseudomonas aeruginosa
The Pseudomonas quinolone system (pqs) is one of the key quorum sensing systems in antibiotic-resistant P. aeruginosa and is responsible for the production of virulence factors and biofilm formation. Thus, synthetic small molecules that can target the PqsR (MvfR) receptor can be utilized as quorum sensing inhibitors to treat P. aeruginosa infections. In this study, we report the synthesis of novel thioether-linked dihydropyrrol-2-one (DHP) analogues as PqsR antagonists. Compound 7g containing a 2-mercaptopyridyl linkage effectively inhibited the pqs system with an IC50 of 32 μM in P. aeruginosa PAO1. Additionally, these inhibitors significantly reduced bacterial aggregation and biofilm formation without affecting planktonic growth. The molecular docking study suggest that these inhibitors bind with the ligand binding domain of the MvfR as a competitive antagonist.
Sabir, Shekh,Suresh, Dittu,Subramoni, Sujatha,Das, Theerthankar,Bhadbhade, Mohan,Black, David StC.,Rice, Scott A.,Kumar, Naresh
Dihydropyrrolones as bacterial quorum sensing inhibitors
Bacteria regulate their pathogenicity and biofilm formation through quorum sensing (QS), which is an intercellular communication system mediated by the binding of signaling molecules to QS receptors such as LasR. In this study, a range of dihydropyrrolone (DHP) analogues were synthesized via the lactone-lactam conversion of lactone intermediates. The synthesized compounds were tested for their ability to inhibit QS, biofilm formation and bacterial growth of Pseudomonas aeruginosa. The compounds were also docked into a LasR crystal structure to rationalize the observed structure-activity relationships. The most active compound identified in this study was compound 9i, which showed 63.1% QS inhibition of at 31.25 μM and 60% biofilm reduction at 250 μM with only moderate toxicity towards bacterial cell growth.
Almohaywi, Basmah,Yu, Tsz Tin,Iskander, George,Chan, Daniel S.H.,Ho, Kitty K.K.,Rice, Scott,Black, David StC.,Griffith, Renate,Kumar, Naresh
p. 1054 - 1059
(2019/03/13)
NOVEL LACTAMS
The present invention relates to novel lactams of formulae (I) and (II). The present invention further relates to the use of these compounds in the treatment of microbial infections and microbial contamination of surfaces, particularly infections and surf
-
Page/Page column 26
(2010/11/28)
More Articles about upstream products of 945538-80-7