Synthesis and Biological Evaluation of Celastrol Derivatives as Potential Immunosuppressive Agents.,Journal of Natural Products

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Synthesis and Biological Evaluation of Celastrol Derivatives as Potential Immunosuppressive Agents.
Journal of Natural Products ( IF 3.3 ) Pub Date : 2020-08-21 , DOI: 10.1021/acs.jnatprod.0c00067
Qi-Wei He ₁ , Jia-Hao Feng ₁ , Xiao-Long Hu ₁ , Huan Long ₁ , Xue-Feng Huang ₁ , Zhen-Zhou Jiang ₂ , Xiao-Qi Zhang ₃ , Wen-Cai Ye ₃ , Hao Wang ₁

Affiliation

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.

中文翻译：

Celastrol 衍生物作为潜在免疫抑制剂的合成和生物学评价。

南蛇藤醇，一木栓型三萜类化合物从属植物中分离雷公藤，具有抗肿瘤，抗炎，免疫抑制和活动。总共合成了 42 种 Celastrol 衍生物（1a – 1t、2a – 2l和3a – 3j）并评估了它们的免疫抑制活性。化合物2a – 2e显示出免疫抑制作用，IC ₅₀值范围为 25 至 83 nM，细胞毒性较弱（CC ₅₀ > 1 μM）。化合物2a选择性指数值比 celastrol 高 31 倍，被选为先导化合物。进一步的研究表明，2a通过 Lck 和 ZAP-70 介导的信号通路诱导细胞凋亡和抑制细胞因子分泌来发挥其免疫抑制作用。

更新日期：2020-09-25

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