title: Benzamidobenzoic acids as potent PqsD inhibitors for the treatment of Pseudomonas aeruginosa infections.
abstract: Targeting PqsD is a promising novel approach to disrupt bacterial cell-to-cell-communication in Pseudomonas aeruginosa. In search of selective PqsD inhibitors, two series of benzamidobenzoic acids - one published as RNAP inhibitors and the other as PqsD inhibitors - were investigated for inhibitory activity toward the respective other enzyme. Additionally, novel derivatives were synthesized and biologically evaluated. By this means, the structural features needed for benzamidobenzoic acids to be potent and, most notably, selective PqsD inhibitors were identified. The most interesting compound of this study was the 3-Cl substituted compound 5 which strongly inhibits PqsD (IC₅₀ 6.2 μM) while exhibiting no inhibition of RNAP.
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland, Department of Drug Design and Optimization, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hinsberger
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland, Department of Drug Design and Optimization, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: de Jong
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland, Department of Drug Design and Optimization, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Groh
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland, Department of Drug Design and Optimization, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Haupenthal
authors.affiliation: Helmholtz-Institute for Pharmaceutical Research Saarland, Department of Drug Design and Optimization, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany; Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany. Electronic address: rwh@mx.uni-saarland.de.
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D001565:Benzoates
keywords: Benzamidobenzoic acid; PqsD inhibitor; PqsD selectivity; Pseudomonas aeruginosa; RNA polymerase inhibitor