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Updated: Mar 2, 2026

Author Spotlight: Advancing Therapeutics to Treat Vibriosis in Humans and Aquatic Organisms
Published on: May 31, 2024
Structure-functionality relationship and pharmacological profiles of Pseudomonas aeruginosa alkylquinolone quorum
Ahmed A M Kamal1, Lucia Petrera, Jens Eberhard
1Helmholtz-Institute for Pharmaceutical Research Saarland, Department of Drug Design and Optimization, Campus E8.1, 66123 Saarbrücken, Germany.
Abstract:
An important paradigm in anti-infective research is the antivirulence concept. Pathoblockers are compounds which disarm bacteria of their arsenal of virulence factors. PqsR is a transcriptional regulator controlling the production of such factors in Pseudomonas aeruginosa, most prominently pyocyanin. In this work, a series of tool compounds based on the structure of the natural ligand 2-heptyl-4-quinolone (HHQ) were used for probing the structure-functionality relationship. Four different profiles are identified namely agonists, antagonists, inverse agonists and biphasic modulators. Molecular docking studies revealed that each class of the PqsR modulators showed distinctive interactions in the PqsR binding domain. It was found that the substituents in position 3 of the quinolone core act as a switch between the different profiles, according to their ability to donate or accept a hydrogen bond, or form a hydrophobic interaction. Finally, it was shown that only inverse agonists were able to strongly inhibit pyocyanin production.
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