title: Glycodiversification for the optimization of the kanamycin class aminoglycosides.
abstract: In an effort to optimize the antibacterial activity of kanamycin class aminoglycoside antibiotics, we have accomplished the synthesis and antibacterial assay of new kanamycin B analogues. A rationale-based glycodiversification strategy was employed. The activity of the lead is comparable to that of commercially available kanamycin. These new members, however, were found to be inactive against aminoglycoside resistant bacteria. Molecular modeling was used to provide the explanation. Thus, a new strategy for structural modifications of kanamycin class aminoglycosides is suggested.
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, Utah 84322-0300, USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Hsiao-Nung
authors.initials: HN
authors.lastname: Chen
authors.forename: Huiwen
authors.initials: H
authors.lastname: Chang
authors.forename: Christabel Tomla
authors.initials: CT
authors.lastname: Tanifum
authors.forename: Hsiu-Hsiang
authors.initials: HH
authors.lastname: Liu
authors.forename: Przemyslaw G
authors.initials: PG
authors.lastname: Czyryca
authors.forename: Cheng-Wei Tom
authors.initials: CW
authors.lastname: Chang
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002240:Carbohydrate Sequence; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects; D007612:Kanamycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019868:Kanamycin Kinase / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012313:RNA / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; C001495:bekanamycin; D007612:Kanamycin; D012313:RNA; D019868:Kanamycin Kinase