title: Novel semisynthetic antibiotics from caprazamycins A-G: caprazene derivatives and their antibacterial activity.
abstract: Acidic treatment of a mixture of caprazamycins (CPZs) A-G isolated from a screen of novel antimycobacterial agents gave caprazene, a core structure of CPZs, in high yield. Chemical modification of the resulting caprazene was performed to give its various derivatives. The structure-activity relationships of the caprazene derivatives against several mycobacterial species and pathogenic Gram-positive and Gram-negative bacteria were studied. Although caprazene showed no antibacterial activity, the antibacterial activity was restored for its 1'''-alkylamide, 1'''-anilide and 1'''-ester derivatives. Compounds 4b (CPZEN-45), 4d (CPZEN-48), 4f and 4g (CPZEN-51) exhibited more potent activities against Mycobacterium tuberculosis and M. avium complex strains than CPZ-B. These results suggest that caprazene would be a good precursor from which novel semisynthetic antibacterial antibiotics can be designed for the treatment of mycobacterial diseases such as tuberculosis and M. avium complex infection.
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Kawasaki, Kanagawa, Japan. takashow@bikaken.or.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Igarashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Miyake
authors.forename: Hiromi
authors.initials: H
authors.lastname: Soutome
authors.forename: Kanae
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Komatsuki
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Koyama
authors.forename: Naoko
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Seiko
authors.initials: S
authors.lastname: Hattori
authors.forename: Kunio
authors.initials: K
authors.lastname: Inoue
authors.forename: Norio
authors.initials: N
authors.lastname: Doi
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Akamatsu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009162:Mycobacterium avium / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001381:Azepines; D008055:Lipids; D009705:Nucleosides; C512217:caprazamycin A; C476914:caprazamycin B; C512218:caprazamycin C; C512219:caprazamycin D; D014529:Uridine