Synthesis and Biological Evaluation of Celastrol Derivatives as Potential Immunosuppressive Agents.

Celastrol, a friedelane-type triterpenoid isolated from the genus Triperygium, possesses antitumor, anti-inflammatory, and immunosuppressive activities. A total of 42 celastrol derivatives (1a-1t, 2a-2l, and 3a-3j) were synthesized and evaluated for their immunosuppressive activities. Compounds 2a-2e showed immunosuppressive effects, with IC50 values ranging from 25 to 83 nM, and weak cytotoxicity (CC50 > 1 μM). Compound 2a, with a selectivity index value 31 times higher than that of celastrol, was selected as a lead compound. Further research showed that 2a exerted its immunosuppressive effects by inducing apoptosis and inhibiting cytokine secretion via Lck- and ZAP-70-mediated signaling pathways.

Citation

Qi-Wei He, Jia-Hao Feng, Xiao-Long Hu, Huan Long, Xue-Feng Huang, Zhen-Zhou Jiang, Xiao-Qi Zhang, Wen-Cai Ye, Hao Wang. Synthesis and Biological Evaluation of Celastrol Derivatives as Potential Immunosuppressive Agents. Journal of natural products. 2020 Sep 25;83(9):2578-2586

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PMID: 32822186

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