Structural correlation between lipophilicity and lipopolysaccharide-sequestering activity in spermine-sulfonamide analogs

Mark R. Burns, Scott A. Jenkins, Nicolas M. Vermeulen, Rajalakshmi Balakrishna, Thuan B. Nguyen, Matthew R. Kimbrell, Sunil A. David

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria, and play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. We had previously defined the pharmacophore necessary for small molecules to specifically bind and neutralize this complex carbohydrate. A series of aryl and aliphatic spermine-sulfonamide analogs were synthesized and tested in a series of binding and cell-based assays in order to probe the effect of lipophilicity on sequestration ability. A strong correlation was indeed found, supporting the hypothesis that endotoxin-neutralizing ability involves a lipophilic or membrane attachment event. The research discussed herein may be useful for the design of additional carbohydrate recognizing molecules and endotoxin-neutralizing drugs.

Original languageEnglish (US)
Pages (from-to)6209-6212
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number24
DOIs
StatePublished - Dec 15 2006

Bibliographical note

Funding Information:
This work was supported from NIH Grant 1U01 AI054785 (S. David).

Keywords

  • Acylpolyamines
  • Endotoxin
  • Lipopolyamines
  • Lipopolysaccharide
  • Sepsis
  • Septic shock

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