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, , , , , , and , 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 , , , , and 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 , , and were protected from lethality induced by coinjection of galactosamine and LPS. Out of eight mice preinjected with 1 mg/kg of compounds , , and , five, eight and six mice were protected, respectively.