Synthesis of N-dialkylphosphoryl iminosugar derivatives and their immunosuppressive activities.
Twelve novel N-dialkylphosphoryliminosugar derivatives were synthesized and their immunosuppressive activities were evaluated on the proliferation of the mouse splenocytes and the secretion of IFN-γ and IL-4. The experimental data demonstrated that the iminosugars with the double long alkyl chains exhibited better inhibitory effects than those with the single long alkyl chain, and the iminosugars with the 10-carbon linear alkyl chain exhibited the strongest immunosuppressive activities. The assay of the cytokine secretion showed that the introduction of dialkyl chains on iminosugars could regulate the polarization of immune inhibition by varying the length of the alkyl chains. The disclosure of the structure-activity relationships may benefit the structural modifications of iminosugars to find new types of immunosuppressive agents.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China. xinshan@bjmu.edu.cn.
Xuemei
X
Yang
De-Cai
DC
Xiong
Chengcheng
C
Song
Guihua
G
Tai
Xin-Shan
XS
Ye
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D050111:Imino Sugars / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000276:immunology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D015394:Molecular Structure; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship
D050111:Imino Sugars; D007166:Immunosuppressive Agents; D015847:Interleukin-4; D007371:Interferon-gamma