Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Bioorg Chem. 2020 Sep;102:104076. doi: 10.1016/j.bioorg.2020.104076. Epub 2020 Jul 7.
A new series of derivatives characterized by the presence of the 3,4,5-trimethoxylbenzamide substituted benzofurans were synthesized and evaluated for antiproliferative activity against four cancer cell lines and one normal human cell line. Among them, derivative 6g with greatest cytotoxicity significantly inhibited the growth of MDA-MB-231, HCT-116, HT-29 and HeLa cell lines with IC values of 3.01, 5.20, 9.13, and 11.09 μM, respectively. Importantly, 6g possessed excellent selectivity over non-tumoral cell lines HEK-293 (IC > 30 μM). Moreover, mechanistic studies revealed that 6g induced HeLa cells arrested in G2/M phase in a concentration-dependent manner, and inhibited polymerization of tubulin via a consistent way with CA-4. In general, these observations suggest that 6g is a promising anti-cancer lead and is worth further investigation to generate potential antitumor agents.
我们合成了一系列以 3,4,5-三甲氧基苯甲酰胺取代苯并呋喃为特征的新型衍生物，并评估了它们对四种癌细胞系和一种正常人类细胞系的抗增殖活性。其中，细胞毒性最强的衍生物 6g 对 MDA-MB-231、HCT-116、HT-29 和 HeLa 细胞系的生长具有显著的抑制作用，IC 值分别为 3.01、5.20、9.13 和 11.09 μM。重要的是，6g 在非肿瘤细胞系 HEK-293 中具有优异的选择性（IC > 30 μM）。此外，机制研究表明，6g 以浓度依赖的方式诱导 HeLa 细胞停滞在 G2/M 期，并通过与 CA-4 一致的方式抑制微管蛋白的聚合。总的来说，这些观察结果表明 6g 是一种很有前途的抗癌先导化合物，值得进一步研究以开发潜在的抗肿瘤药物。
