Design, synthesis, and antiproliferative and CDK2-cyclin A inhibitory activity of novel flavopiridol analogues

被引：37

作者：

Ahn, Yu Mi

Vogeti, Lakshminarayana

Liu, Chun-Jing

Santhapuram, Hari K. R.

White, Jonathan M.

Vasandani, Veena

Mitscher, Lester A.

Lushington, Gerald H.

Hanson, Paul R.

Powell, Douglas R.

Himes, Richard H.

Roby, Katherine F.

Ye, Qizhuang

Georg, Gunda I.

机构：

[1] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA

[2] Univ Kansas, High Throughput Screening Lab, Lawrence, KS 66045 USA

[3] Univ Kansas, Dept Chem, Lawrence, KS 66045 USA

[4] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA

[5] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66160 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 02期

关键词：

flavopiridol analogues; synthesis; cytotoxicity; CDK2-cyclin A; docking simulations;

D O I：

10.1016/j.bmc.2006.10.063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The design and synthesis of a small library of 8-amidoflavone, 8-sulfonamidoflavone, 8-amido-7-hydroxyflavone, and heterocyclic analogues of flavopiridol is reported. The potential activity of these compounds as kinase inhibitors was evaluated by cytotoxicity studies in MCF-7 and ID-8 cancer cell lines and inhibition of CDK2-Cyclin A enzyme activity in vitro. The anti-proliferative and CDK2-Cyclin A inhibitory activity of these analogues was significantly lower than the activity of flavopiridol. Molecular docking simulations were carried out and these studies suggested a different binding orientation inside the CDK2 binding pocket for these analogues compared to flavopiridol. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：702 / 713

页数：12

共 33 条

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