IGARASHI M, NAKAGAWA N, HATTORI S, DOI N, MASUDA T, YAMAZAKI T, MIYAKE T, NAGANAWA H, ISHIZUKA M, SHOMURA T, OMOTO S, YANO I, HAMADA M, TAKEUCHI T; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. F-2031.
Institute of Microbial Chemistry, Tokyo, Japan.
BACKGROUND: Novel nucleoside anti-TB antibiotics, caprazamycins A-F, were found in a culture broth of Streptomyces sp.MK730-62F2. METHODS: Caprazamycins (CPZs) were purified by Diaion HP20 and silicagel column chromatographies and HPLC. The structures of CPZs were determined spectroscopically and by degradation studies. The anti-TB activities of CPZs were measured either by agar-dilution or broth-dilution methods. RESULTS: CPZ-B(major component), C[53]H[87]N[5]O[22], mw 1145, showed strong activity not only against TB reference strains but also against clinically isolated strains. The MICs of CPZ-B were; 3.13microg/ml for Mycobacterium tuberculosis H37Rv, ravenel and kurono strains and 6.25-12.5microg/ml for M. tuberculosis (n=20). Further, CPZ-B exhibited strong activity against atypical mycobacteria. The MICs of CPZ-B were; 0.05-0.39microg/ml for M. avium (n=3) and 0.78 microg/ml for M. intracelulare E-1 NIHJ-1618. According to cross resistance experiments, the mode of action of CPZ-B was found to be different from those of current anti-TB drugs. In the pulmonary tuberculosis model with H37Rv in mice (n=6), CPZ-B showed a therapeutic effect at 1.5mg/kg/day by intranasal administration. CPZ-B did not show any toxicities in mice even at 200 mg/kg (acute) and 100 mg/kg/day (subacute, 14 days) by subcutaneous injection. CONCLUSIONS: CPZs were found to possess strong activity against tuberculotic and atypical mycobacterial strains. The efficacy and safety in mice warranted further evaluation of CPZs. Structure-activity relationships of CPZ components are now under study.
Publication Types:
Keywords:
- Animals
- Anti-Bacterial Agents
- Mice
- Microbial Sensitivity Tests
- Mycobacteria, Atypical
- Mycobacterium tuberculosis
- Streptomyces
- Tuberculosis, Pulmonary
Other ID:
UI: 102267657
From Meeting Abstracts