Naphthalimides exhibit in vitro antiproliferative and antiangiogenic activities by inhibiting both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs)

• Novel naphthalimide derivatives were synthesized.
• The compounds were topo II inhibitors and showed good antiproliferative activity.
• For the first time, naphthalimides were proved to be tyrosine kinase inhibitors.
• 8d displayed effective antiangiogentic activity by inhibiting tyrosine kinases.

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.

A novel series of naphthalimides were synthesized. Several of them could inhibit both topo II and angiogenesis-related receptor tyrosine kinases. The representative compound 8d not only was potent antiproliferative agent, but also exhibited effective antiangiogenic activity at 10 μMFigure optionsDownload as PowerPoint slide