N-苄氧羰基甘氨酰-L-脯氨酸-鬼臼毒素衍生物的合成及其抗肿瘤活性

以鬼臼毒素（podophyllotoxin）、N-苄氧羰基甘氨酰-L-脯氨酸为原料，首次合成了10个新型鬼臼毒素衍生物（Ⅲa～Ⅲi、Ⅳ），目标化合物结构经1H NMR、13C NMR和MS确认。采用MTT法测试化合物Ⅲa～Ⅲi和Ⅳ对HepG2、THP-1、HeLa、MCF-7细胞的抑制活性。结果表明：所有目标化合物均具有不同程度的抑制活性，其中化合物Ⅲa对HepG2细胞的活性最突出，IC50达0.58 nmol/L。通过分子对接模拟技术进一步研究了化合物Ⅲa和FAPα酶的结合模式，Ⅲa可以与FAPα酶的多个位点产生相互作用，值得进一步研究其抗肿瘤机制。

Synthesis and anti-tumor activity of Z-Gly-Pro-OH-podophyllotoxin derivatives

Ten novel podophyllotoxin derivatives(Ⅲa-Ⅲi and Ⅳ)were synthesized by three-step reactions using podophyllotoxin and N-benzyloxycarbonyl glycine-L-proline as raw material.The structures of the target compounds were confirmed by ¹H NMR,¹³C NMR and MS.MTT method was used to test anti-tumor activity of the target compounds on HepG2,THP-1,HeLa and MCF-7 cells.The results showed that all the target compounds had inhibitory activity against HepG2,THP-1,HeLa and MCF-7 cells,and the inhibitory activity of Ⅲa on HepG2 cells was the most prominent with an IC₅₀ value of 0.58 nmol/L.The binding mode of compound Ⅲa and FAPαwas studied by molecular docking.Compound Ⅲa could bind to multiple sites of FAPαenzyme.