Synthesis of lipid A analogues containing glucose instead of glucosamine and their LPS-antagonistic activities |
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Authors: | Masao Shiozaki Yukiko Watanabe Toshio Kaneko Daisuke Tanaka Shin-ichi Kurakata |
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Institution: | a Chemistry Department, Chemtech Labo Inc., Hiromachi 1-2-58, Shinagawa-ku, Tokyo 140-8710, Japan b Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., Hiromachi 1-2-58, Shinagawa-ku, Tokyo 140-8710, Japan c Biological Research Laboratories, Sankyo Co., Ltd., Hiromachi 1-2-58, Shinagawa-ku, Tokyo 140-8710, Japan |
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Abstract: | Lipid A analogues containing glucose in substitution for glucosamine on the reducing end were synthesized, and the inhibitory activities on LPS-induced TNFα production (LPS-antagonistic activity) in vitro using human whole blood cells were measured. The IC50 values (nM) of these ten compounds, 8, 14, 21, 31, 40, 51, 57, 62, 67 and 72, were 11.2, 15.4, 2.7, 0.1, 0.4, 1.3, 3.2, 3.2, 1.4 and 14.4, respectively. And also inhibitory activities (ID50) on TNFα production toward galactosamine loaded C3H/HeN mice in vivo of compounds 21, 31, 57, 62 and 67 were measured. The values of these compounds were 0.29, 0.50, 0.61, not dose-dependent and 0.33 mg/kg, respectively. |
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Keywords: | LPS-antagonist RsDPLA |
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