Polycationic sulfonamides for the sequestration of endotoxin

Mark R. Burns, Scott A. Jenkins, Matthew R. Kimbrell, Rajalakshmi Balakrishna, Thuan B. Nguyen, Benjamin G. Abbo, Sunil A. David

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Lipopolysaccharides (LPS) play a key role in the pathogenesis of septic shock, a major cause of mortality in the critically ill patient. We had previously shown that monoacylated polyamine compounds specifically bind to and neutralize the activity of LPS with high in vitro potency and afford complete protection in a murine model of endotoxic shock. Fatty acid amides of polyamines may be rapidly cleared from systemic circulation due to their susceptibility to nonspecific serum amidases and, thus, would be predicted to have a short duration of action. In a systematic effort to increase the likelihood of better bioavailability properties together with structural modifications that may result in gains in activity, we now report structure-activity relationships pertaining to endotoxin-binding and -neutralizing activities of homologated polyamine sulfonamides.

Original languageEnglish (US)
Pages (from-to)877-888
Number of pages12
JournalJournal of medicinal chemistry
Issue number4
StatePublished - Feb 22 2007


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