Synthesis and Modeling of New Benzofuranone Histone Deacetylase Inhibitors that Stimulate Tumor Suppressor Gene Expression

被引：50

作者：

Charrier, Cedric ^{[1
]}

Clarhaut, Jonathan ^{[2
]}

Gesson, Jean-Pierre ^{[1
]}

Estiu, Guillermina ^{[3
]}

Wiest, Olaf ^{[3
]}

Roche, Joelle ^{[2
]}

Bertrand, Philippe ^{[1
]}

机构：

[1] Univ Poitiers, Lab Synth & React Subst Nat, CNRS, UMR 6514, F-86022 Poitiers, France

[2] Univ Poitiers, Inst Physiol & Biol Cellulaires, CNRS, UMR 6187, F-86022 Poitiers, France

[3] Univ Notre Dame, Walther Canc Res Center, Dept Chem & Biochem, Notre Dame, IN 46556 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 09期

关键词：

CRYSTAL-STRUCTURE; LUNG-CANCER; SAHA; SELECTIVITY; MECHANISM; HOMOLOG; DESIGN;

D O I：

10.1021/jm9002439

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New benzofuranones were synthesized and evaluated toward NCI-H661 non-small cell lung cancer cells. Benzamide derivatives possessed micromolar anti proliferative and histone deacetylase inhibitory activities and modulate histone H4 acetylation. Hydroxamic acids were found to be potent nanomolar anti proliferative agents and HDAC inhibitors. Computational analysis presented a rationale for the activities of the hydroxamate derivatives. Impact of the HDAC inhibition on the expression of E-cadherin and the SEMA3F tumor suppressor genes revealed new promising compounds for lung cancer treatments.

引用

页码：3112 / 3115

页数：4

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