Nitrogen-containing flavonoids as CDK1/Cyclin B inhibitors: design, synthesis, and biological evaluation.
A novel series of nitrogen-containing flavonoids 5a-l, 6a,b, and 7a,b were designed and synthesized as cyclin-dependent kinases (CDKs) inhibitors. The representative compounds 5a, 5b, 5e, and 5g showed potent CDK1/Cyclin B inhibitory activities. All compounds displayed a significant growth inhibitory action in vitro against Bel-7402, PC-3, ECA-109, A-549, HL-60, and MCF-7 cancer cell lines. Flow cytometry analysis showed that 5b induced apoptosis in PC-3 cells.
Liu
Tao
T
ZJU-ENS Joint Laboratory of Medicinal Chemistry, School of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, PR China.
Xu
Zhongmiao
Z
He
Qiaojun
Q
Chen
Yanhong
Y
Yang
Bo
B
Hu
Yongzhou
Y
D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019926:Cyclin B / Q000037:antagonists & inhibitors*; D015195:Drug Design; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009584:Nitrogen / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D019926:Cyclin B; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D016203:CDC2 Protein Kinase; D009584:Nitrogen