A New PqsR Inverse Agonist Potentiates Tobramycin Efficacy to Eradicate Pseudomonas aeruginosa Biofilms.

ABSTRACT: Pseudomonas aeruginosa (PA) infections can be notoriously difficult to treat and are often accompanied by the development of antimicrobial resistance (AMR). Quorum sensing inhibitors (QSI) acting on PqsR (MvfR) - a crucial transcriptional regulator serving major functions in PA virulence - can enhance antibiotic efficacy and eventually prevent the AMR. An integrated drug discovery campaign including design, medicinal chemistry-driven hit-to-lead optimization and in-depth biological profiling of a new QSI generation is reported. The QSI possess excellent activity in inhibiting pyocyanin production and PqsR reporter-gene with IC₅₀ values as low as 200 and 11 × 10^-9 m, respectively. Drug metabolism and pharmacokinetics (DMPK) as well as safety pharmacology studies especi

SUBMITTER: Schutz C 

PROVIDER: S-EPMC8224453 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature