Novel semisynthetic antibiotics from caprazamycins A-G: caprazene derivatives and their antibacterial activity.
Yoshiaki Takahashi,Masayuki Igarashi,Toshiaki Miyake,Hiromi Soutome,Kanae Ishikawa,Yasuhiro Komatsuki,Yoshiko Koyama,Naoko Nakagawa,Seiko Hattori,Kunio Inoue,Norio Doi,Yuzuru Akamatsu +11 more
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TLDR
The 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.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.read more
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