title: Rational design and synthesis of potent aminoglycoside antibiotics against resistant bacterial strains.
abstract: Based on the structural information of biomacromolecule-aminoglycoside complexes, a series of kanamycin B analogues were rationally designed and synthesized. A convenient approach to the construction of kanamycin derivatives, in which the C4'-position on ring I of neamine moiety was modified, was developed. Most synthetic analogues exhibited good to excellent antibiotic activity against some typical drug-resistant bacteria. The disclosed results suggested that the C4'-position of aminoglycosides such as kanamycin may be an ideal site for modification to gain new modifying enzyme-resistant aminoglycoside antibiotics.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China.
authors.forename: Ri-Bai
authors.initials: RB
authors.lastname: Yan
authors.forename: Min
authors.initials: M
authors.lastname: Yuan
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Wu
authors.forename: Xuefu
authors.initials: X
authors.lastname: You
authors.forename: Xin-Shan
authors.initials: XS
authors.lastname: Ye
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002240:Carbohydrate Sequence; D015195:Drug Design; D004352:Drug Resistance, Microbial; D008958:Models, Molecular; D008969:Molecular Sequence Data
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents