State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Eur J Med Chem. 2013 Jul;65:477-86. doi: 10.1016/j.ejmech.2013.05.002. Epub 2013 May 14.
Novel naphthalimide derivatives were designed and synthesized to modulate both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs). Most target compounds exhibited effective and selective antiproliferative activities against three cancer cell lines by inhibiting topo II. The IC50 values ranged from 1.5 to 19.1 μM. Moreover, compounds 8d and 12d moderately inhibited various angiogenesis-related RTKs, including FGFR1, VEGFR2 and PDGFRα. The representative compound 8d was then proved to possess antiangiogenic activity, which was evidenced by the inhibition of migration and tube formation activities of HMEC-1 cells. To our knowledge, it is the first time naphthalimides were identified as tyrosine kinases inhibitors (TKIs) besides their conventional cytotoxicity.
新型萘酰亚胺衍生物被设计和合成，以调节拓扑异构酶 II（topo II）和受体酪氨酸激酶（RTKs）。大多数目标化合物通过抑制拓扑异构酶 II 对三种癌细胞系表现出有效的和选择性的抗增殖活性。IC50 值范围为 1.5 到 19.1 μM。此外，化合物 8d 和 12d 适度抑制各种与血管生成相关的 RTKs，包括 FGFR1、VEGFR2 和 PDGFRα。代表性化合物 8d 随后被证明具有抗血管生成活性，这表现在抑制 HMEC-1 细胞的迁移和管形成活性。据我们所知，这是首次发现萘酰亚胺除了传统的细胞毒性之外，还可以作为酪氨酸激酶抑制剂（TKIs）。
