Structure-activity relationships of lipopolysaccharide sequestration in N-alkylpolyamines

Anurupa Shrestha, Diptesh Sil, Subbalakshmi S. Malladi, Hemamali J. Warshakoon, Sunil A. David

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


We have previously shown that simple N-acyl or N-alkyl polyamines bind to and sequester Gram-negative bacterial lipopolysaccharide, affording protection against lethality in animal models of endotoxicosis. Several iterative design-and-test cycles of SAR studies, including high-throughput screens, had converged on compounds with polyamine scaffolds which have been investigated extensively with reference to the number, position, and length of acyl or alkyl appendages. However, the polyamine backbone itself had not been explored sufficiently, and it was not known if incremental variations on the polymethylene spacing would affect LPS-binding and neutralization properties. We have now systematically explored the relationship between variously elongated spermidine [NH2-(CH2)3-NH-(CH2) 4-NH2] and norspermidine [NH2-(CH2)3-NH-(CH2) 3-NH2] backbones, with the N-alkyl group being held constant at C16 in order to examine if changing the spacing between the inner secondary amines may yield additional SAR information. We find that the norspermine-type compounds consistently showed higher activity compared to corresponding spermine homologues.

Original languageEnglish (US)
Pages (from-to)2478-2481
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number9
StatePublished - May 1 2009

Bibliographical note

Funding Information:
Funding from the NIH (1U01AI077947) is gratefully acknowledged.


  • Endotoxin
  • Lipopolyamines
  • Lipopolysaccharide
  • N-Alkylpolyamines
  • Sepsis
  • Sequestration


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