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

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.

• Authors: Stephen A Cochrane, Xuefeng Li, Sisi He, Min Yu, Min Wu, John C Vederas
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 58 Issue 24 Pg. 9779-85 (Dec 24 2015) ISSN: 1520-4804 [Electronic] United States
• PMID: 26636619 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Bacterial Agents
• Peptides
• tridecaptins
• Erythromycin
• Vancomycin
• Rifampin

Topics

• Acinetobacter baumannii (drug effects)
• Animals
• Anti-Bacterial Agents (chemical synthesis, pharmacology)
• Drug Synergism
• Erythromycin (analogs & derivatives, chemical synthesis, pharmacology)
• Escherichia coli (drug effects)
• Gram-Negative Bacteria (drug effects)
• Klebsiella Infections (drug therapy)
• Klebsiella pneumoniae (drug effects)
• Mice, Inbred C57BL
• Microbial Sensitivity Tests
• Peptides (chemical synthesis, pharmacology)
• Rifampin (analogs & derivatives, chemical synthesis, pharmacology)
• Vancomycin (analogs & derivatives, chemical synthesis, pharmacology)