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ID: ALA1139003
Journal: Bioorg Med Chem Lett
Title: Novel endotoxin-sequestering compounds with terephthalaldehyde-bis-guanylhydrazone scaffolds.
Authors: Khownium K, Wood SJ, Miller KA, Balakrishna R, Nguyen TB, Kimbrell MR, Georg GI, David SA.
Abstract: 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.
CiteXplore: 16377188