目的 设计、合成固醇调控元件结合蛋白（SREBP）抑制剂BF-175的衍生物，并对其稳定性和体外抗肿瘤活性进行研究。方法 以水杨醛为起始原料，通过6步反应合成了一系列含硼小分子SREBP抑制剂，通过高效液相色谱法分析其稳定性，并采用RT-PCR实验评价其抗肿瘤活性。结果 合成了9个含硼小分子SREBP抑制剂，并通过NMR和MS对其进行表征。其药学稳定性均优于BF-175。RT-PCR检测表明目标化合物可以抑制人子宫内膜腺癌细胞（AN3CA）中SREBP靶基因硬脂酰辅酶A去饱和酶-1（SCD-1）的表达，其中化合物7g的活性高于BF-175。结论 含硼小分子SREBP抑制剂具有较好的抗肿瘤活性，为此类药物的作用机制研究奠定了基础。

Objective To design and synthetize derivatives of sterol regulatory element-binding proteins (SREBP) inhibitor BF-175, and study their stabilities and antitumor activities in vitro. Methods Taking salicylaldehyde as the starting material, a series of SREBP inhibitors were synthesized by a six-step reaction. Their stabilities were analyzed by HPLC, and their antitumor activities were evaluated by RT-PCR. Results Nine SREBP inhibitors were synthesized. Their structures were characterized by NMR and MS, and their pharmaceutical stabilities were superior to BF-175. RT-PCR results showed that the compounds could inhibit the expression of SREBP target gene stearoyl-CoA desaturase-1 (SCD-1), and compound 7g had higher activity than BF-175. Conclusion SREBP inhibitors have good antitumor activity, which laid the foundation for the study of the mechanism of these drugs.

R914;R966

中央高校基本科研业务费专项资金资助（3332018117）；中国医学科学院医学与健康科技创新工程项目资助（2016-I2M-3-022、2017-I2M-3-019）；天津市科技计划项目资助（18ZXXYSY00110）；天津市自然科学基金项目资助（18JCQNJC09500）