A series of novel hydantoin-bridged analogues of combretastatin A-4 (CA-4) were designed, synthesized and evaluated for antiproliferative activities in vitro and in vivo. The most potent compound 8d, showed potent cytotoxicity against four human cancer cell lines with IC₅₀ values of 0.186–0.279 μM, and possessed the efficacy of inhibiting tubulin polymerization, disrupting in vitro vascularization, blocking cell cycle in G₂/M phase and inducing cell apoptosis. In the nude mice xenograft model, 8d significantly inhibited the tumor growth and showed low toxicity. Further chiral separation proved (R)-(−)-8d to be the preferential enantiomer with IC₅₀ values of 0.081–0.157 M. These results indicated that the hydantoin derivatives merit further investigation as potential anticancer agents that inhibit tubulin polymerization.

设计，合成并评估了康布雷他汀A-4（CA-4）的一系列新的乙内酰脲桥联类似物在体外和体内的抗增殖活性。最强效的化合物8d对4种人类癌细胞系表现出强大的细胞毒性，IC ₅₀值为0.186–0.279μM，并具有抑制微管蛋白聚合，破坏体外血管形成，阻断G ₂ / M期细胞周期并诱导细胞凋亡的功效。细胞凋亡。在裸鼠异种移植模型中，8d显着抑制肿瘤生长并显示出低毒性。进一步的手性分离证明（R）-（-）- 8d它们是IC ₅₀值为0.081-0.157 M的优先对映体。这些结果表明，乙内酰脲衍生物作为抑制微管蛋白聚合的潜在抗癌剂值得进一步研究。