Synthesis of N‐Substituted Iminosugar Derivatives and Evaluation of Their Immunosuppressive Activities

Abstract

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, (3R,4S)-1-(4-heptyloxylphenylethyl)pyrrolidine-3,4-diol and (3R,4S)-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 =2.16 and 2.48 μm, 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.

Synthesis of modified 1,5-imino-d-xylitols as ligands for lysosomal β-glucocerebrosidase

“…Many different naturally occurring structures are known, exceeded by the number of synthetic derivatives, with manifold different modification patterns concerning the carbohydrate scaffold as well as customized derivatisations for different applications. This substance class has been implicated as potential therapeutic agents [ 6 ], for example, as immunomodulators [ 7 , 8 ], as antibacterial [ 9 , 10 ], antiviral [ 11 , 12 ], anti-cancer [ 13 ], and anti-fungal [ 14 ] agents. In addition, iminoalditol-based glycomimetics have been identified as plant growth inhibitors [ 15 ].…”