A series of (E)-N-Aryl-2-oxo-2-(3,4,5-trimethoxyphenyl)acetohydrazonoyl cyanides have been synthesized and evaluated for their anticancer activity in human hepatocellular liver carcinoma HepG2 and breast adenocarcinoma MCF-7 cell lines. Among all the tested compounds, compound 3a, 3e and 3n displayed more activity than lead compound with IC₅₀ value of 0.26–0.61 μM. Meanwhile, these compounds (3a, 3e and 3n) showed potent antiproliferative activity against a panel of cancer cells and the HCT-8/T multidrug resistant cell line with IC₅₀ values in the range of 0.077– 7.44 μM. Flow cytometric analyses revealed that compound 3n induced cell cycle arrest in G2/M phases in a dose dependent manner. The compound 3n also displayed potent tubulin polymerization inhibition with an IC₅₀ value of 0.9 µM, with ten folds more active than colchicine (IC₅₀ = 9 μM). Molecular docking studies revealed that compound 3n efficiently interacted with the colchicine binding site of tubulin through hydrophobic, cation-π and hydrogen bond interaction. Furthermore, in silico pharmacokinetic prediction shown that these compounds have a good ADME-related physicochemical parameters. These results demonstrate that 3n exhibits potent cytotoxicity in cancer cells by targeting the colchicine binding site of tubulin and potentially acts as a therapeutic lead compound for the development of anticancer drugs.

合成了一系列（E）-N-Aryl-2-oxo-2-（3,4,5-三甲氧基苯基）乙酰肼基酰氰化物，并评估了其在人肝细胞肝癌HepG2和乳腺癌中的抗癌活性MCF-7细胞线。在所有测试化合物中，化合物3a，3e和3n的活性均高于铅化合物，IC ₅₀值为0.26-0.61μM。同时，这些化合物（3a，3e和3n）对一组癌细胞和HCT-8 / T多药耐药细胞系显示有效的抗增殖活性，IC ₅₀值在0.077至7.44μM之间。流式细胞仪分析表明该化合物3n诱导的细胞周期阻滞于G2 / M期，呈剂量依赖性。化合物3n还显示出有效的微管蛋白聚合抑制作用，IC ₅₀值为0.9 µM，活性比秋水仙碱高十倍（IC ₅₀  = 9 µM）。分子对接研究表明，化合物3n通过疏水，阳离子-π和氢键相互作用与微管蛋白的秋水仙碱结合位点有效相互作用。此外，计算机计算机动力学预测表明，这些化合物具有良好的ADME相关的理化参数。这些结果表明3n 通过靶向微管蛋白的秋水仙碱结合位点，在癌细胞中具有强的细胞毒性，并有可能作为开发抗癌药物的治疗先导化合物。