苯磺酰胺类IDO1抑制剂的设计、合成和生物活性

基金项目: 国家自然科学基金资助项目(No.21472244,No.21472091,No.21772233) ^#金双龙和王芳对本论文的贡献相同

Design, synthesis and biological evaluation of phenylsulfonamide-based IDO1 inhibitors

摘要: 在IDO1抑制剂 U - 3i 的基础上，利用生物电子等排原理，结合分子对接技术，设计并合成了11个苯磺酰胺类目标化合物。采用基于HeLa细胞的酶学测定方法评价了目标化合物对IDO1活性的影响，结果表明，大多数化合物对IDO1显示不同程度的抑制活性。其中，化合物 3b 和 3e 的抑制作用最强，而且能够逆转IDO1介导的免疫抑制，值得进一步研究。
- IDO1抑制剂 /
- 苯磺酰胺 /
- 合成 /
- 生物活性
Abstract: Based on the reported IDO1 inhibitor U - 3i , 11 phenylsulfonamide derivatives were designed and synthesized by adopting bioisosterism and molecular docking technology. The inhibitory activities of the target compounds against IDO1 were determined by the HeLa cell-based kynurenine assay. The results demonstrated that most compounds showed different degrees of inhibitory effects on IDO1. Among them, compounds 3b and 3e displayed the most potent activity and could reverse IDO1-mediated immune suppression, which might be worth of further investigation.
- IDO1 inhibitor /
- phenylsulfonamide /
- synthesis /
- biological evaluation

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