Hits:

Indexed by:期刊论文

Date of Publication:2008-08-01

Journal:BIOORGANIC & MEDICINAL CHEMISTRY

Included Journals:SCIE、PubMed、Scopus

Volume:16

Issue:15

Page Number:7127-7132

ISSN No.:0968-0896

Key Words:flavonoid analogues; baicalein; CDK1/cyclin B inhibitor; SAR

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 mu M) were about sixfold more potent than baicalein 2 (IC(50) 6.53 mu M). 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 mu M) were about 20-fold more potent than baicalein, and were at the same level as flavopiridol (IC(50) 0.33 mu M). (C) 2008 Elsevier Ltd. All rights reserved.