Beta-carbolines as specific inhibitors of cyclin-dependent kinases.
Harmine (3), 7-fluoro-1-methyl beta-carboline (35) and 1-(5-methyl-imidazol-4-yl) beta-carboline (41) were potent and specific inhibitors of cyclin-dependent kinases. The degree of aromaticity of the tricyclic ring and the positioning of substituents are important for inhibitory activity. While most beta-carbolines inhibited CDK2 and CDK5 to the same extent, selective inhibition against CDK2 was observed in 1-(2-chlorophenyl)- (12), 1-(2-fluorophenyl)- (15), and 1-(2-chloro-5-nitrophenyl)- (28) beta-carbolines.
Song
Yongcheng
Y
Medicinal and Combinatorial Chemistry Group, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Singapore.
Wang
Jian
J
Teng
Su Fern
SF
Kesuma
Djohan
D
Deng
Yu
Y
Duan
Jinao
J
Wang
Jerry H
JH
Qi
Robert Zhong
RZ
Sim
Mui Mui
MM
D042846:CDC2-CDC28 Kinases; D002243:Carbolines / Q000494:pharmacology*; D051357:Cyclin-Dependent Kinase 2; D051360:Cyclin-Dependent Kinase 5; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
D002243:Carbolines; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases