摘要/Abstract

为了探索具有新型骨架的抗癌剂, 设计了一系列的以环丙烷限制构象的双酰胺类化合物. 大多数含有顺式环丙烷中心的外消旋体对四种肿瘤细胞系(MCF-7、BGC-823、HepG2和NCI-H460)具有良好的抑制活性. 其中, 消旋体顺式-N¹-(2-甲基-4-(全氟丙-2-基)苯基)-N²-(4-苯氧基苄基)环丙烷-1,2-二羧酰胺(1-19)对MCF-7的IC₅₀值为(8.38±0.67) mg•L^–1, 显示出可进一步优化为抗癌先导物的潜力. 此外, 甾醇硫酸酯酶(steryl-sulfatase, STS)被PharmMapper预测为可能的靶标蛋白, 并由分子对接实验进行了验证.
关键词: 双酰胺, 环丙烷, 抗癌活性, 靶标预测, 分子对接
A series of diamides conformationally restricted by cyclopropane were designed and synthesized. Most of the racemates containing cis-cyclopropane possessed promising inhibitory activity against four cancer cell lines (MCF-7, BGC-823, HepG2 and NCI-H460). In particular, racemate cis-N¹-(2-methyl-4-(perfluoropropan-2-yl)phenyl)-N²-(4-phenoxy- benzyl)cyclopropane-1,2-dicarboxamide (1-19) showed the potential for further optimization as an anti-cancer lead with the IC₅₀ value of (8.38±0.67) mg•L^–1 on MCF-7. Moreover, steryl-sulfatase (STS) was predicated as the potential target protein and molecular docking was performed to explore the binding mode.
Key words: diamides, cyclopropane, anti-cancer activities, target prediction, docking


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