Gemini compounds of the type Nα,Nω-bis(Nα-lauroyl arginine)α,ω-alkylenediamides or bis(Args) bind bacterial lipopolysaccharide and neutralize endotoxic activity in in vitro tumor necrosis factor-α and nitric oxide release assays. Sequestration of lipopolysaccharide results in protection in a murine model of endotoxemia. However, the bis(Args) compounds are cytotoxic by virtue of being highly membrane-active. The development of less surface-active analogues may yield potentially therapeutically useful compounds for the treatment of Gram-negative sepsis.
Bibliographical noteFunding Information:
This was supported by the MEC, project PPQ2000-1687-CO2-01.