Structural correlation between lipophilicity and lipopolysaccharidesequestering activity in spermine-sulfonamide analogs

[摘要] 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. (c) 2006 Elsevier Ltd. All rights reserved.

[发布日期] 2006-12-15

[关键词] lipopolysaccharide;sepsis;septic shock;endotoxin;acylpolyamines;lipopolyan-tines