Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 15, Issue 13, Pages 4528-4536Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2007.04.024
Keywords
apoptosis; enediyne; G2/M phase arrest; cyclin A; Cdc25C
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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 mu M) and MDA-MB-435 (0.8 mu M), 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. (c) 2007 Elsevier Ltd. All rights reserved.
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