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Synthesis of N‐Substituted Iminosugar Derivatives and Evaluation of Their Immunosuppressive Activities
Author(s) -
Lv Zhuo,
Song Chengcheng,
Niu Youhong,
Li Qin,
Ye XinShan
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700706
Subject(s) - iminosugar , pyrrolidine , splenocyte , chemistry , inhibitory postsynaptic potential , stereochemistry , amide , diol , pharmacology , medicine , biochemistry , in vitro , organic chemistry , enzyme
It is important to find more effective and safer immunosuppressants, because clinically used immunosuppressive agents have significant side effects. A series of N‐substituted iminosugar derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK‐8 assay. The results revealed that iminosugars 10 e and 10 i , that is, (3 R ,4 S )‐1‐(4‐heptyloxylphenylethyl)pyrrolidine‐3,4‐diol and (3 R ,4 S )‐1‐[2‐(2‐chloro‐4‐( p ‐tolylthio)‐phenyl‐1‐yl)ethyl]pyrrolidine‐3,4‐diol, respectively, exhibited the strongest inhibitory effects on mouse splenocyte proliferation (IC 50 =2.16 and 2.48 μ m , respectively), whereas the iminosugars containing an amide group near the hydrophilic head (compounds 10 j – n ) exhibited no inhibitory effects. Further studies revealed that the inhibitory effects on splenocyte proliferation may have come from the suppression of both IFN‐γ and IL‐4 cytokines. Our results suggest that synthetic iminosugars, especially compounds 10 e and 10 i , hold potential as immunosuppressive agents.