title: Structure-activity relationship of 4(5)-aryl-2-amino-1H-imidazoles, N1-substituted 2-aminoimidazoles and imidazo[1,2-a]pyrimidinium salts as inhibitors of biofilm formation by Salmonella typhimurium and Pseudomonas aeruginosa.
abstract: A library of 112 4(5)-aryl-2-amino-1H-imidazoles, 4,5-diphenyl-2-amino-1H-imidazoles, and N1-substituted 4(5)-phenyl-2-aminoimidazoles was synthesized and tested for the antagonistic effect against biofilm formation by Salmonella Typhimurium and Pseudomonas aeruginosa. The substitution pattern of the 4(5)-phenyl group and the nature of the N1-substituent were found to have a major effect on the biofilm inhibitory activity. The most active compounds of this series were shown to inhibit the biofilm formation at low micromolar concentrations. Furthermore, the influence of 6 imidazo[1,2-a]pyrimidines and 18 imidazo[1,2-a]pyrimidinium salts on the biofilm formation was tested. These compounds are the chemical precursors of the 2-aminoimidazoles in our synthesis pathway. A good correlation was found between the activity of the imidazo[1,2-a]pyrimidinium salts and their corresponding 2-aminoimidazoles, supporting the hypothesis that the imidazo[1,2-a]pyrimidinium salts are possibly cleaved by cellular nucleophiles to form the active 2-aminoimidazoles. However, the imidazo[1,2-a]pyrimidines did not show any biofilm inhibitory activity, indicating that these molecules are not susceptible to in situ degradation to 2-aminoimidazoles. Finally, we demonstrated the lack of biofilm inhibitory activity of an array of 37 2N-substituted 2-aminopyrimidines, which are the chemical precursors of the imidazo[1,2-a]pyrimidinium salts in our synthesis pathway.
authors.affiliation: Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Kasteelpark Arenberg 20, B-3001 Leuven, Belgium.
authors.forename: Hans P L
authors.initials: HP
authors.lastname: Steenackers
authors.forename: Denis S
authors.initials: DS
authors.lastname: Ermolat'ev
authors.forename: Bharat
authors.initials: B
authors.lastname: Savaliya
authors.forename: Ami
authors.initials: A
authors.lastname: De Weerdt
authors.forename: David
authors.initials: D
authors.lastname: De Coster
authors.forename: Anamik
authors.initials: A
authors.lastname: Shah
authors.forename: Erik V
authors.initials: EV
authors.lastname: Van der Eycken
authors.forename: Dirk E
authors.initials: DE
authors.lastname: De Vos
authors.forename: Jozef
authors.initials: J
authors.lastname: Vanderleyden
authors.forename: Sigrid C J
authors.initials: SC
authors.lastname: De Keersmaecker
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D007093:Imidazoles; D011743:Pyrimidines