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 (0.4microM) and MDA-MB-435 (0.8microM), 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.
Lo
Yu-Hsiang
YH
Graduate Institute of Pharmaceutical Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lin
I-Ling
IL
Lin
Chi-Fong
CF
Hsu
Cheng-Chung
CC
Yang
Sheng-Huei
SH
Lin
Shinne-Ren
SR
Wu
Ming-Jung
MJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019925:Cyclin A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D007202:Indicators and Reagents; D021281:Quantitative Structure-Activity Relationship; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D019925:Cyclin A; D007202:Indicators and Reagents; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D020169:Caspases