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

Abstract 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.