title: The requirements at the C-3 position of alkylquinolones for signalling in Pseudomonas aeruginosa.
abstract: The 'perfect storm' of increasing bacterial antibiotic resistance and a decline in the discovery of new antibiotics, has made it necessary to search for new and innovative strategies to treat bacterial infections. Interruption of bacterial cell-to-cell communication signalling (Quorum Sensing), thus neutralizing virulence in pathogenic bacteria, is a growing area. 2-Alkyl-4-quinolones, HHQ and PQS, play a key role in the quorum sensing circuitry of P. aeruginosa. We report a new set of isosteres of 2-heptyl-6-nitroquinolin-4-one, with alterations at C-3, and evaluate the key structural requirements for agonistic and antagonistic activity in Pseudomonas aeruginosa.
authors.affiliation: Department of Chemistry and Analytical & Biological Chemistry Research Facility (ABCRF), University College Cork, Ireland. g.mcglacken@ucc.ie.
authors.forename: Rachel
authors.initials: R
authors.lastname: Shanahan
authors.affiliation: BIOMERIT Research Centre, Department of Microbiology, University College Cork, Ireland. f.ogara@ucc.ie.
authors.forename: F Jerry
authors.initials: FJ
authors.lastname: Reen
authors.affiliation: Department of Chemistry and Analytical & Biological Chemistry Research Facility (ABCRF), University College Cork, Ireland. g.mcglacken@ucc.ie.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cano
authors.affiliation: BIOMERIT Research Centre, Department of Microbiology, University College Cork, Ireland. f.ogara@ucc.ie and School of Biomedical Sciences, CHIRI, Curtin University, Perth WA 6845, Australia.
authors.forename: Fergal
authors.initials: F
authors.lastname: O'Gara
authors.affiliation: Department of Chemistry and Analytical & Biological Chemistry Research Facility (ABCRF), University College Cork, Ireland. g.mcglacken@ucc.ie.
authors.forename: Gerard P
authors.initials: GP
authors.lastname: McGlacken
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D053038:Quorum Sensing / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D015363:Quinolones