title: Synthesis and antimicrobial evaluation of nitazoxanide-based analogues: identification of selective and broad spectrum activity.
abstract: A library composed of nitazoxanide-based analogues was synthesized and assayed for increased antibacterial efficacy against the pyruvate-ferredoxin oxidoreductase (PFOR) using microorganisms Helicobacter pylori, Campylobacter jejuni and Clostridium difficile. Derivatives were found to recapitulate and improve activity against these organisms and select analogues were tested for their ability to disrupt the PFOR enzyme directly. The library was also screened for activity against staphylococci and resulted in the identification of analogues capable of inhibiting both staphylococci and all PFOR organisms at low micromolar minimum inhibitory concentrations with low toxicity to human foreskin cells.
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville, VA 22904-4319, USA. teb2m@virginia.edu
authors.forename: T Eric
authors.initials: TE
authors.lastname: Ballard
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Igor
authors.initials: I
authors.lastname: Olekhnovich
authors.forename: Taylor
authors.initials: T
authors.lastname: Koerner
authors.forename: Craig
authors.initials: C
authors.lastname: Seymour
authors.forename: Joseph
authors.initials: J
authors.lastname: Salamoun
authors.forename: Michelle
authors.initials: M
authors.lastname: Warthan
authors.forename: Paul S
authors.initials: PS
authors.lastname: Hoffman
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Macdonald
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009574:Nitro Compounds; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D009574:Nitro Compounds; D013844:Thiazoles; C041747:nitazoxanide