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个人信息Personal Information
教授
博士生导师
硕士生导师
性别：男
毕业院校：大连理工大学
学位：博士
所在单位：生物工程学院
学科：生物化工. 生物化学与分子生物学. 生物工程与技术
办公地点：大连理工大学生物工程楼323；盘锦校区D06 302室
联系方式：E-mail:biosci@dlut.edu.cn Tel:13332280036
电子邮箱：biosci@dlut.edu.cn
Nitrogen-containing flavonoid analogues as CDK1/cyclin B inhibitors: Synthesis, SAR analysis, and biological activity
点击次数：
论文类型：期刊论文
发表时间：2008-08-01
发表刊物：BIOORGANIC & MEDICINAL CHEMISTRY
收录刊物：SCIE、PubMed、Scopus
卷号：16
期号：15
页面范围：7127-7132
ISSN号：0968-0896
关键字：flavonoid analogues; baicalein; CDK1/cyclin B inhibitor; SAR
摘要：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.