Structure-activity relationships of globomycin analogues as antibiotics.
Globomycin (1a), a signal peptidase II inhibitor, and its derivatives show potent antibacterial activity against Gram-negative bacteria. The synthesis and antimicrobial activity of novel globomycin analogues are reported. The hydroxyl group in the L-Ser residue was essential for the antimicrobial activity and the length of the alkyl side chain greatly influenced the activity. In addition, derivatives that had a modified cyclic core exhibited weak activity. One of the analogues showed a wider antimicrobial spectrum, effective against not only Gram-negative but also Gram-positive bacteria.
Kiho
Toshihiro
T
Exploratory Chemistry Research Laboratories, Sankyo Co. Ltd., 2-58 Hiromachi 1-chome, Sinagawa-ku, Tokyo 140-8710, Japan.
Nakayama
Mizuka
M
Yasuda
Kayo
K
Miyakoshi
Shunichi
S
Inukai
Masatoshi
M
Kogen
Hiroshi
H
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001671:Biochemistry / Q000379:methods; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D010455:Peptides; C017339:globomycin