Naphthalimide intercalators with chiral amino side chains: Effects of chirality on DNA binding, photodamage and antitumor cytotoxicity

被引：50

作者：

Yang, Qing ^{[1
]}

Yang, Peng ^{[1
]}

Qian, Xuhong ^{[3
]}

Tong, Lianpeng ^{[2
]}

机构：

[1] Dalian Univ Technol, Dept Biosci & Biotechnol, Dalian 116012, Liaoning, Peoples R China

[2] Dalian Univ Technol, State Key Lab Fine Chem, Dalian 116012, Peoples R China

[3] E China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 23期

基金：

中国国家自然科学基金;

关键词：

Antitumor agents; Chirality; Naphthalimide; DNA intercalation; DNA photodamage;

D O I：

10.1016/j.bmcl.2008.09.104

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several novel heterocyclic-fused naphthalimides intercalators with chiral amino side chains were investigated. Their side chains' chiral configuration determines DNA binding activities in the order: S-enantiomers > R-enantiomers. And their DNA photodamaging activities were in good agreement with their DNA binding constants, the S-enantiomers could photocleave circular supercoiled pBR322 DNA more ef.ciently than their R-enantiomers. S-enantiomer B-3 could photodamage DNA at 0.2 mu M and cleave supercoiled plasmid DNA from form I to form II completely at 50 mu M. Almost all of these intercalators showed effective cytoxicities against human lung cancer cells and murine leukemia cells. S-enantiomers showed different antitumor cytotoxicity by comparison with R-enantiomers. This work may provide additional information for the role of amino side chains on intercalators as antitumor agents. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：6210 / 6213

页数：4

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