Small-Molecule Inhibitors of the NusB-NusE Protein-Protein Interaction with Antibiotic Activity.

ABSTRACT: The NusB-NusE protein-protein interaction (PPI) is critical to the formation of stable antitermination complexes required for stable RNA transcription in all bacteria. This PPI is an emerging antibacterial drug target. Pharmacophore-based screening of the mini-Maybridge compound library (56 000 molecules) identified N,N'-[1,4-butanediylbis(oxy-4,1-phenylene)]bis(N-ethyl)urea 1 as a lead of interest. Competitive enzyme-linked immunosorbent assay screening validated 1 as a 20 μM potent inhibitor of NusB-NusE. Four focused compound libraries based on 1, comprising 34 compounds in total were designed, synthesized, and evaluated as NusB-NusE PPI inhibitors. Ten analogues displayed NusB-NusE PPI inhibition ≥50% at 25 μM concentration in vitro. In contras

SUBMITTER: Cossar PJ 

PROVIDER: S-EPMC6044933 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature