title: Nitrogen-containing flavonoid analogues as CDK1/cyclin B inhibitors: synthesis, SAR analysis, and biological activity.
abstract: A series of nitrogen-containing flavonoid analogues were designed and synthesized by Mannich reaction, and screened for the inhibitory activities of cyclin-dependent kinases using a FRET-based biochemical assay method. The results showed that C-8 nitrogen-containing baicalein analogues 3a-3f exhibited potent CDK1/Cyclin B inhibitory activities. 5,6,7-Trihydroxy-8-(dimethylaminomethyl)-2-phenyl-4H-chromen-4-one 3a, 5,6,7-trihydroxy-8-(pyrrolid inylmethyl)-2-phenyl-4H-chromen-4-one 3b, and 5,6,7-trihydroxy-8-(piperidinylmethyl)-2-phenyl-4H-chromen-4-one 3c (IC(50) 1.05-1.28 microM) were about sixfold more potent than baicalein 2 (IC(50) 6.53 microM). 5,6,7-Trihydroxy-8-(morpholinomethyl)-2-phenyl-4H-chromen-4-one 3d, 5,6,7-trihydroxy-8-(thiomorpholinomethy)-2-phenyl-4H-chrom en-4-one 3e, and 5,6,7-trihydroxy-8-(4-methylpiperazinylmethyl)-2-phenyl-4H-chromen-4-one 3f (IC(50) 0.27-0.38 microM) were about 20-fold more potent than baicalein, and were at the same level as flavopiridol (IC(50) 0.33 microM).
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Zhongshan Road 158-90, Dalian 116012, PR China. zhangsx56@yahoo.com.cn
authors.forename: Shixuan
authors.initials: S
authors.lastname: Zhang
authors.forename: Jigang
authors.initials: J
authors.lastname: Ma
authors.forename: Yongming
authors.initials: Y
authors.lastname: Bao
authors.forename: Puwen
authors.initials: P
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Zou
authors.forename: Kangjian
authors.initials: K
authors.lastname: Li
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D019926:Cyclin B / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D009584:Nitrogen / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D019926:Cyclin B; D005419:Flavonoids; D016203:CDC2 Protein Kinase; D009584:Nitrogen