Hepatocellular carcinoma (HCC) is a major global cause of carcinoma-related fatality. The inhibition of tubulin polymerization holds significant potential in the development of cancer drugs. In our study, we synthesized a novel pyrrolidine-2,5-dione derivative (compound 8) that exhibited potent anti-HCC activity (IC₅₀ value of 2.082 μM) against human HCC HepG2 cells. Moreover, compound 8 significantly suppressed the HepG2 cell multiplication, and triggered G2/M phase arrest of HepG2 cells and their apoptosis. Further mechanistic investigations revealed that compound 8 suppressed tubulin polymerization by directly binding to the colchicine binding site of β-tubulin. Additionally, compound 8 significantly inhibited tumor growth with low toxicity in nude HepG2 tumor-bearing mice, achieving an approximate inhibition rate of 45.73 %. Therefore, compound 8 represents a promising pharmaceutical candidate for HCC management.

肝细胞癌（HCC）是全球癌症相关死亡的主要原因。微管蛋白聚合的抑制在癌症药物的开发中具有巨大的潜力。在我们的研究中，我们合成了一种新型吡咯烷-2,5-二酮衍生物（化合物8），它对人HCC HepG2细胞表现出有效的抗HCC活性（IC ₅₀值为2.082 μM）。此外，化合物8显着抑制HepG2细胞增殖，并引发HepG2细胞的G2/M期阻滞及其凋亡。进一步的机理研究表明，化合物8通过直接结合到β-微管蛋白的秋水仙碱结合位点来抑制微管蛋白聚合。此外，化合物8对HepG2荷瘤裸鼠的肿瘤生长具有显着的低毒抑制作用，抑制率约为45.73%。因此，化合物8代表了用于HCC治疗的有前途的候选药物。