Synthesis of Tridecaptin-Antibiotic Conjugates with in Vivo Activity against Gram-Negative Bacteria

Stephen A Cochrane, Xuefeng Li, Sisi He, Min Yu, Min Wu, John C Vederas

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

A series of tridecaptin-antibiotic conjugates were synthesized and evaluated for in vitro and in vivo activity against Gram-negative bacteria. Covalently linking unacylated tridecaptin A1 (H-TriA1) to rifampicin, vancomycin, and erythromycin enhanced their activity in vitro but not by the same magnitude as coadministration of the peptide and these antibiotics. The antimicrobial activities of the conjugates were retained in vivo, with the H-TriA1-erythromycin conjugate proving a more effective treatment of Klebseilla pneumoniae infections in mice than erythromycin alone or in combination with H-TriA1.

Original languageEnglish
Pages (from-to)9779-85
Number of pages7
JournalJournal of Medicinal Chemistry
Volume58
Issue number24
Early online date04 Dec 2015
DOIs
Publication statusPublished - 24 Dec 2015

Keywords

  • Acinetobacter baumannii
  • Animals
  • Anti-Bacterial Agents
  • Drug Synergism
  • Erythromycin
  • Escherichia coli
  • Gram-Negative Bacteria
  • Klebsiella Infections
  • Klebsiella pneumoniae
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Peptides
  • Rifampin
  • Vancomycin
  • Journal Article
  • Research Support, N.I.H., Extramural

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