title: Identification and characterization of 4-[4-(3-phenyl-2-propen-1-yl)-1-piperazinyl]-5H-pyrimido[5,4-b]indole derivatives as Salmonella biofilm inhibitors.
abstract: A screening of a small-molecule library was conducted, in search of Salmonella biofilm inhibitors active in a broad temperature range, both in prevention and in eradication of biofilms. Moreover, the inhibitors were selected not to influence the planktonic growth of Salmonella to diminish the selective pressure and to prevent or slow down resistance development. Out of the 20,014 compounds screened at 16 and 37 °C, 140 hits were identified. After characterization of the most promising hits at a broader set of temperatures (16, 25, 30 and 37 °C), we identified 7-methoxy-4-[4-(3-phenyl-2-propen-1-yl)-1-piperazinyl]-5H-pyrimido[5,4-b]indole as an interesting preventive anti-biofilm compound. A first structure-activity relationship of this compound was delineated, revealing 8-fluoro-4-[4-(3-phenyl-2-propen-1-yl)-1-piperazinyl]-5H-pyrimido[5,4-b]indole as a promising analogue in the prevention of Salmonella biofilms.
authors.affiliation: Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KU Leuven, Heverlee, Belgium.
authors.forename: Stijn Chris Arnold
authors.initials: SC
authors.lastname: Robijns
authors.forename: Bart
authors.initials: B
authors.lastname: De Pauw
authors.forename: Bram
authors.initials: B
authors.lastname: Loosen
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchand
authors.forename: Patrick
authors.initials: P
authors.lastname: Chaltin
authors.forename: Sigrid C J
authors.initials: SC
authors.lastname: De Keersmaecker
authors.forename: Jos
authors.initials: J
authors.lastname: Vanderleyden
authors.forename: Hans P L
authors.initials: HP
authors.lastname: Steenackers
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D050296:Microbial Viability / Q000187:drug effects; D012475:Salmonella / Q000187:drug effects* / Q000502:physiology*; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D007211:Indoles