title: Anti-bacterial glycosyl triazoles - Identification of an N-acetylglucosamine derivative with bacteriostatic activity against Bacillus.
abstract: N-acetylglucosaminidases (GlcNAcases) play an important role in the remodeling and recycling of bacterial peptidoglycan. Inhibitors of bacterial GlcNAcases can serve as antibacterial agents and provide an opportunity for the development of new antibiotics. We report the synthesis of triazole derivatives ofN-acetylglucosamine using a copper promoted azide-alkyne coupling reaction between 1-azido-N-acetylglucosamine and a small library of terminal alkynes prepared via the Ugi reaction. These compounds were evaluated for their ability to inhibit the growth of bacteria. Two compounds that show bacteriostatic activity againstBacilluswere identified, with MIC values of approximately 60 μM in both cases.Bacillus subtiliscultured in the presence of sub-MIC amounts of the glycosyl triazole inhibitors exhibit an elongated phenotype characteristic of impaired cell division. This represents the first report of inhibitors of bacterial cell wall GlcNAcases that demonstrate inhibition of cell growth in whole cell assays.
authors.affiliation: Department of Chemistry, Brown University, Providence RI 02912; Department of Science and Technology, Bryant University, Providence RI 02917.
authors.forename: Helene
authors.initials: H
authors.lastname: Kuhn
authors.affiliation: Department of Chemistry, Brown University, Providence RI 02912; Department of Science and Technology, Bryant University, Providence RI 02917.
authors.forename: Danielle
authors.initials: D
authors.lastname: Gutelius
authors.affiliation: Department of Chemistry, Brown University, Providence RI 02912; Department of Science and Technology, Bryant University, Providence RI 02917.
authors.forename: Eimear
authors.initials: E
authors.lastname: Black
authors.affiliation: Department of Chemistry, Brown University, Providence RI 02912; Department of Science and Technology, Bryant University, Providence RI 02917.
authors.forename: Christina
authors.initials: C
authors.lastname: Nadolny
authors.affiliation: Department of Chemistry, Brown University, Providence RI 02912; Department of Science and Technology, Bryant University, Providence RI 02917.
authors.forename: Amit
authors.initials: A
authors.lastname: Basu
authors.affiliation: Department of Chemistry, Brown University, Providence RI 02912; Department of Science and Technology, Bryant University, Providence RI 02917.
authors.forename: Christopher
authors.initials: C
authors.lastname: Reid