title: Beta-carbolines as specific inhibitors of cyclin-dependent kinases.
abstract: 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.
authors.affiliation: Medicinal and Combinatorial Chemistry Group, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Singapore.
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Song
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Su Fern
authors.initials: SF
authors.lastname: Teng
authors.forename: Djohan
authors.initials: D
authors.lastname: Kesuma
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.forename: Jinao
authors.initials: J
authors.lastname: Duan
authors.forename: Jerry H
authors.initials: JH
authors.lastname: Wang
authors.forename: Robert Zhong
authors.initials: RZ
authors.lastname: Qi
authors.forename: Mui Mui
authors.initials: MM
authors.lastname: Sim
mesh_terms: 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*
chemical_list: 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