Syntheses of glucose-containing E5564 analogues and their LPS-antagonistic activities

Lipid A analogues containing a glucose moiety on their non-reducing end were synthesized, and their LPS-antagonistic activities were measured. The inhibitory activities (IC₅₀) on LPS-induced TNFα production of these six compounds, 26, 33, 44β, 52β, 59, and 61, toward human whole blood cells were 0.49, 0.65, 0.51, 0.98, 0.46, and 1.11 nM, respectively. Inhibitory doses (ID₅₀) of compounds 26, 33, 44β, 59, and 61 on TNFα production induced by coinjection of galactosamine and LPS in C3H/HeN mice were measured. The ID₅₀ values of these compounds were 0.45, 0.96, <0.2, 1.08, and <0.2 mg/kg, respectively. Moreover, C3H/HeN mice preinjected with compounds 26, 33, and 44β were protected from lethality induced by coinjection of galactosamine and LPS. Out of eight mice preinjected with 1 mg/kg of compounds 26, 33, and 44β, five, eight and six mice were protected, respectively.