Novel acyclic enediynes inhibit Cyclin A and Cdc25C expression and induce apoptosis phenomenon to show potent antitumor proliferation

A series of acyclic enediynes showing significant inhibition on the growth of tumor cancer is disclosed. To investigate the structure–activity relationship, compounds 12–33 were synthesized. Among them, compound 17 showed most potent growth inhibition activity against all tumor cell lines at low concentration, such as SR (0.4 μM) and MDA-MB-435 (0.8 μM), and almost completely blocked cell cycle in G2/M phase via controlling Cyclin A and Cdc25C expression. On the other hand, compound 29 showed potent induced apoptosis activity by inducing activation of caspase-3, -8, and -9. Thus, this article disclosed a new multiple-protein regulator in cell cycle regulation and induced apoptosis to achieve the goal of anticancer drug.

Enediynes showed most potent growth inhibition activity against all tumor cell lines in low concentration and almost completely blocked cell cycle in G2/M phase via controlling Cyclin A and Cdc25C expression and apoptosis.Figure optionsDownload as PowerPoint slide