Novel endotoxin-sequestering compounds with terephthalaldehyde-bis- guanylhydrazone scaffolds

Kriangsak Khownium, Stewart J. Wood, Kelly A. Miller, Rajalakshmi Balakrishna, Thuan B. Nguyen, Matthew R. Kimbrell, Gunda I. Georg, Sunil A. David

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


We have shown that lipopolyamines bind to the lipid A moiety of lipopolysaccharide, a constituent of Gram-negative bacterial membranes, and neutralize its toxicity in animal models of endotoxic shock. In an effort to identify non-polyamine scaffolds with similar endotoxin-recognizing features, we had observed an unusually high frequency of hits containing guanylhydrazone scaffolds in high-throughput screens. We now describe the syntheses and preliminary structure-activity relationships in a homologous series of bis-guanylhydrazone compounds decorated with hydrophobic functionalities. These first-generation compounds bind and neutralize lipopolysaccharide with a potency comparable to that of polymyxin B, a peptide antibiotic known to sequester LPS.

Original languageEnglish (US)
Pages (from-to)1305-1308
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number5
StatePublished - Mar 1 2006

Bibliographical note

Funding Information:
This work was supported by NIH 1U01 AI 56476. K.K. is grateful to the Royal Thai Government for a scholarship from the Development and Promotion of Science and Technology (DPST) Project. Coordinates of models of the compounds docked on lipid A are available on request.


  • Bis-guanylhydrazones
  • Endotoxin
  • Lipopolysaccharide
  • Sepsis


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