Studies on novel bacterial translocase I inhibitors, A-500359s. II. Biological activities of A-500359 A, C, D and G.

A-500359 A, C, D, G and capuramycin inhibited bacterial phospho-N-acetylmuramyl-pentapeptide-translocase (translocase I: EC with IC50 values of 0.017, 0.12, 0.53, 0.14 and 0.018 microM, respectively. Consistently, A-500359 A, C and capuramycin inhibited in vitro peptidoglycan biosynthesis. A-500359 A exhibited reversible inhibition, which was mixed type and noncompetitive with respect to UDP-MurNAc-(N(epsilon)-Dns)pentapeptide (Ki=0.0079 microM) and undecaprenyl-phosphate, respectively. A-500359 A, C, D and G showed antimicrobial activity against Mycobacterium smegmatis. As a single intravenous injection of A-500359 A at a dose of 500 mg/kg showed no toxicity in mice, it was suggested that the capuramycin derivatives might become candidates as novel therapeutic agents for various diseases caused by Mycobacteria including tuberculosis.
AuthorsYasunori Muramatsu, Michiko Miyazawa Ishii, Masatoshi Inukai
JournalThe Journal of antibiotics (J Antibiot (Tokyo)) Vol. 56 Issue 3 Pg. 253-8 (Mar 2003) ISSN: 0021-8820 [Print] Japan
PMID12760681 (Publication Type: Journal Article)
Chemical References
  • Aminoglycosides
  • Anti-Bacterial Agents
  • Azepines
  • Enzyme Inhibitors
  • capuramycin
  • Transferases (Other Substituted Phosphate Groups)
  • phospho-N-acetylmuramoyl pentapeptide transferase
  • Uridine
  • Aminoglycosides
  • Animals
  • Anti-Bacterial Agents (chemistry, pharmacology, toxicity)
  • Azepines (chemistry, pharmacology, toxicity)
  • Bacteria (enzymology)
  • Enzyme Inhibitors (chemistry, pharmacology, toxicity)
  • Kinetics
  • Mice
  • Microbial Sensitivity Tests
  • Mycobacterium smegmatis (drug effects)
  • Transferases (Other Substituted Phosphate Groups)
  • Uridine (analogs & derivatives, chemistry, pharmacology, toxicity)

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