title: Synthesis and antibacterial activity of doxycycline neoglycosides.
abstract: A set of 37 doxycycline neoglycosides were prepared, mediated via a C-9 alkoxyamino-glycyl-based spacer reminiscent of that of tigecycline. Subsequent in vitro antibacterial assays against representative drug-resistant Gram negative and Gram positive strains revealed a sugar-dependent activity profile and one doxycycline neoglycoside, the 2'-amino-α-D-glucoside conjugate, to rival that of the parent pharmacophore. In contrast, the representative tetracycline-susceptible strain E. coli 25922 was found to be relatively responsive to a range of doxycycline neoglycosides. This study also extends the use of aminosugars in the context of neoglycosylation via a simple two-step strategy anticipated to be broadly applicable for neoglycorandomization.
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.forename: Larissa V
authors.initials: LV
authors.lastname: Ponomareva
authors.forename: Karen
authors.initials: K
authors.lastname: Marchillo
authors.forename: Maoquan
authors.initials: M
authors.lastname: Zhou
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004318:Doxycycline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D006027:Glycosides; D000078304:Tigecycline; D008911:Minocycline; D004318:Doxycycline