目的 設(shè)計(jì)、合成固醇調(diào)控元件結(jié)合蛋白（SREBP）抑制劑BF-175的衍生物，并對其穩(wěn)定性和體外抗腫瘤活性進(jìn)行研究。方法 以水楊醛為起始原料，通過6步反應(yīng)合成了一系列含硼小分子SREBP抑制劑，通過高效液相色譜法分析其穩(wěn)定性，并采用RT-PCR實(shí)驗(yàn)評價(jià)其抗腫瘤活性。結(jié)果 合成了9個(gè)含硼小分子SREBP抑制劑，并通過NMR和MS對其進(jìn)行表征。其藥學(xué)穩(wěn)定性均優(yōu)于BF-175。RT-PCR檢測表明目標(biāo)化合物可以抑制人子宮內(nèi)膜腺癌細(xì)胞（AN3CA）中SREBP靶基因硬脂酰輔酶A去飽和酶-1（SCD-1）的表達(dá)，其中化合物7g的活性高于BF-175。結(jié)論 含硼小分子SREBP抑制劑具有較好的抗腫瘤活性，為此類藥物的作用機(jī)制研究奠定了基礎(chǔ)。

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

中央高校基本科研業(yè)務(wù)費(fèi)專項(xiàng)資金資助（3332018117）；中國醫(yī)學(xué)科學(xué)院醫(yī)學(xué)與健康科技創(chuàng)新工程項(xiàng)目資助（2016-I2M-3-022、2017-I2M-3-019）；天津市科技計(jì)劃項(xiàng)目資助（18ZXXYSY00110）；天津市自然科學(xué)基金項(xiàng)目資助（18JCQNJC09500）