Design and synthesis of diketopiperazine and acyclic analogs related to the caprazamycins and liposidomycins as potential antibacterial agents.
A systematic simplification methodology of a class of 6'-N-alkyl-5'-O-aminoribosyl-glycyluridine antibiotics was shown to produce potential antibacterial agents having a novel mechanism of action. Diketopiperazines and acyclic analogs of the caprazamycins (CPZs) and liposidomycins (LPMs) were efficiently synthesized, and their antibacterial activity was evaluated. The diketopiperazine analog 11a and the acyclic analogs 12a and 16a having a palmitoyl group as a lipophilic side chain exhibited moderate antibacterial activities with MICs of 12.5-50 microg/mL. This approach could provide ready access to a range of analogs for the development of potential antibacterial agents.
Hirano
Shinpei
S
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Ichikawa
Satoshi
S
Matsuda
Akira
A
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology; D054659:Diketopiperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D008055:Lipids; D008826:Microbial Sensitivity Tests; D009705:Nucleosides; D013329:Structure-Activity Relationship; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001381:Azepines; D054659:Diketopiperazines; D008055:Lipids; D009705:Nucleosides; C512217:caprazamycin A; C476914:caprazamycin B; C512218:caprazamycin C; C512219:caprazamycin D; C047544:liposidomycins; D014529:Uridine