title: Benzimidazole-based antibacterial agents against Francisella tularensis.
abstract: Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90% growth inhibition at 1 μg/mL. Among those hits, 21 compounds showed MIC90 values in the range of 0.35-48.6 μg/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2-3log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 μg/mL.
authors.affiliation: Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Kunal
authors.initials: K
authors.lastname: Kumar
authors.forename: Divya
authors.initials: D
authors.lastname: Awasthi
authors.forename: Seung-Yub
authors.initials: SY
authors.lastname: Lee
authors.forename: Jason E
authors.initials: JE
authors.lastname: Cummings
authors.forename: Susan E
authors.initials: SE
authors.lastname: Knudson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Slayden
authors.forename: Iwao
authors.initials: I
authors.lastname: Ojima
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D005604:Francisella tularensis / Q000187:drug effects* / Q000254:growth & development; D057166:High-Throughput Screening Assays; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001562:Benzimidazoles; D054852:Small Molecule Libraries