Synthesis and Evaluation of Serinolamide Derivatives as Sphingosine-1-Phosphate-1 (S1P1) Receptor Agonists.

Sun Jun Park, Jushin Kim, Jaehwan Kim, Yoowon Kim, Elijah Hwejin Lee, Hyeon Jeong Kim, Siwon Kim, Byungeun Kim, Rium Kim, Ji Won Choi, Jong-Hyun Park, Ki Duk Park

Molecules (Basel, Switzerland) 2022 Apr 28

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Sphingosine-1-phosphate-1 (S1P1) receptor agonists are well-known drugs for treating multiple sclerosis (MS) caused by autoreactive lymphocytes that attack the myelin sheath. Therefore, an effective therapeutic strategy is to reduce the lymphocytes in the blood by inducing S1P1 receptor internalization. We synthesized serinolamide A, a natural product of the sea, and performed S1P1 receptor internalization assay to evaluate functionally antagonistic S1P1 receptor agonist activity. In order to synthesize derivatives with better efficacy than serinolamide A and B, new derivatives were synthesized by introducing the phenyl ring moiety of fingolimod. Among them, compounds 19 and 21 had superior S1P1 agonistic effects to serinolamide. We also confirmed that compound 19 effectively inhibited lymphocyte outflow in peripheral lymphocyte count (PLC) assay.

Citation

Sun Jun Park, Jushin Kim, Jaehwan Kim, Yoowon Kim, Elijah Hwejin Lee, Hyeon Jeong Kim, Siwon Kim, Byungeun Kim, Rium Kim, Ji Won Choi, Jong-Hyun Park, Ki Duk Park. Synthesis and Evaluation of Serinolamide Derivatives as Sphingosine-1-Phosphate-1 (S1P1) Receptor Agonists. Molecules (Basel, Switzerland). 2022 Apr 28;27(9)