Department of Hepatobiliary Surgery, China Medical University, The First People's Hospital of Kunshan, Suzhou, P. R. China.
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, P. R. China.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2247579. doi: 10.1080/14756366.2023.2247579.
Angiogenesis plays an important role in tumour generation and progression, which is used to supply nutrients and metastasis. Herein, a series of novel dihydro-1-indene derivatives were designed and evaluated as tubulin polymerisation inhibitors by binding to colchicine site, exhibiting anti-angiogenic activities against new vessel forming. Through structure-activity relationships study, compound was found to be the most potent derivative possessing the antiproliferative activity against four cancer lines with IC values among 0.028-0.087 M. Compound bound to colchicine site on tubulin and inhibited tubulin polymerisation . In addition, compound induced cell cycle arrest at G2/M phase, stimulated cell apoptosis, inhibited tumour metastasis and angiogenesis. Finally, the results of assay suggested that compound could prevent tumour generation, inhibit tumour proliferation and angiogenesis without obvious toxicity. Collectively, all these findings suggested that compound is a novel tubulin polymerisation inhibitor deserving further research.
血管生成在肿瘤的发生和发展中起着重要作用，它用于提供营养物质和转移。在此，设计了一系列新型二氢-1-茚满衍生物，并通过与秋水仙碱结合位点结合来评估其作为微管蛋白聚合抑制剂的活性，表现出对新血管形成的抗血管生成活性。通过构效关系研究，发现化合物 是最有效的衍生物，对四种癌细胞系具有抗增殖活性，IC 值在 0.028-0.087 μM 之间。化合物 与微管蛋白上的秋水仙碱结合位点结合，抑制微管蛋白聚合。此外，化合物 诱导细胞周期 G2/M 期阻滞，刺激细胞凋亡，抑制肿瘤转移和血管生成。最后， 试验结果表明，化合物 能够预防肿瘤的发生，抑制肿瘤的增殖和血管生成，而没有明显的毒性。综上所述，这些发现表明化合物 是一种新型的微管蛋白聚合抑制剂，值得进一步研究。
