Polycationic sulfonamides for the sequestration of endotoxin
| Autor: | Rajalakshmi Balakrishna, Mark R. Burns, Sunil A. David, Benjamin G. Abbo, Scott Jenkins, Matthew R. Kimbrell, Thuan B. Nguyen |
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| Rok vydání: | 2007 |
| Předmět: |
Lipopolysaccharides
Spermine Pharmacology In Vitro Techniques Nitric Oxide chemistry.chemical_compound Mice Structure-Activity Relationship In vivo Cations Drug Discovery medicine Structure–activity relationship Animals Humans Sulfonamides Septic shock NF-kappa B medicine.disease In vitro Bioavailability Biochemistry chemistry Shock (circulatory) Molecular Medicine Cytokines Female medicine.symptom Polyamine |
| Zdroj: | Journal of medicinal chemistry. 50(4) |
| ISSN: | 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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