Naphthalimides exhibit in vitro antiproliferative and antiangiogenic activities by inhibiting both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs).
Naphthalimides exhibit in vitro antiproliferative and antiangiogenic activities by inhibiting both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs).
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DOI：
10.1016/j.ejmech.2013.05.002
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发表时间：
2013-07
影响因子：
6.7
通讯作者：
Xin Wang;Zhuo Chen;Lin-jiang Tong;Shaoying Tan;Wei Zhou;Ting Peng;Kun Han;Jian Ding;Hua Xie
中科院分区：
文献类型：
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作者：
Xin Wang;Zhuo Chen;Lin-jiang Tong;Shaoying Tan;Wei Zhou;Ting Peng;Kun Han;Jian Ding;Hua Xie
设计并合成了一种新型的萘酰亚胺类化合物，可同时调节拓扑异构酶II(Topo II)和受体酪氨酸激酶(RTK)。大多数目标化合物通过抑制Topo II对三种肿瘤细胞株表现出有效和选择性的抗增殖活性，IC50值在1.5~19.1kgM之间。此外，化合物8d和12d中等程度地抑制了多种血管生成相关的RTK，包括FGFR1VEGFR2和PDGFFRα。具有代表性的化合物8d随后被证明具有抗血管生成活性，这一点从抑制HMEC-1细胞的迁移和管状形成活性得到证明。据我们所知，除了传统的细胞毒性外，这是第一次将萘亚胺类化合物鉴定为酪氨酸激酶抑制剂(TKIs)。
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 IC50values ranged from 1.5 to 19.1 μM. Moreover, compounds8dand12dmoderately inhibited various angiogenesis-related RTKs, including FGFR1, VEGFR2 and PDGFRα. The representative compound8dwas 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.