Glycodiversification for the optimization of the kanamycin class aminoglycosides.
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.
Wang
Jinhua
J
Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, Utah 84322-0300, USA.
Li
Jie
J
Chen
Hsiao-Nung
HN
Chang
Huiwen
H
Tanifum
Christabel Tomla
CT
Liu
Hsiu-Hsiang
HH
Czyryca
Przemyslaw G
PG
Chang
Cheng-Wei Tom
CW
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
D000900:Anti-Bacterial Agents; C001495:bekanamycin; D007612:Kanamycin; D012313:RNA; D019868:Kanamycin Kinase