Abstract

A series of tertiary sulphonamide derivatives were synthesised and evaluated for their antiproliferative activity against liver cancer cell lines (SNU-475, HepG-2, and Bel-7402). Among these tertiary sulphonamides, compound 17a displayed the best anti-liver cancer activity against Bel-7402 cells with an IC₅₀ value of 0.32 μM. Compound 17a could effectively inhibit tubulin polymerisation with an IC₅₀ value of 1.27 μM. Meanwhile, it selectively suppressed LSD1 with an IC₅₀ value of 63 nM. It also concentration-dependently inhibited migration against Bel-7402 cells. Importantly, tertiary sulphonamide 17a exhibited the potent antitumor activity in vivo. All these findings revealed that compound 17a might be a tertiary sulphonamide-based dual inhibitor of tubulin polymerisation and LSD1 to treat liver cancer.

 抽象的

合成了一系列叔磺酰胺衍生物，并评估了它们对肝癌细胞系（SNU-475、HepG-2 和 Bel-7402）的抗增殖活性。在这些三级磺酰胺中，化合物17a对Bel-7402细胞表现出最好的抗肝癌活性，IC ₅₀值为0.32 μM。化合物17a可有效抑制微管蛋白聚合，IC ₅₀值为1.27 μM。同时，它选择性抑制LSD1，IC ₅₀值为63 nM。它还以浓度依赖性方式抑制 Bel-7402 细胞的迁移。重要的是，叔磺酰胺17a在体内表现出有效的抗肿瘤活性。所有这些发现表明，化合物17a可能是一种基于三级磺酰胺的微管蛋白聚合和 LSD1 双重抑制剂，可用于治疗肝癌。