9-N-substituted berberine derivatives:: Stabilization of G-quadruplex DNA and down-regulation of oncogene c-myc

被引：122

作者：

Ma, Yan ^{[1
]}

Ou, Tian-Miao ^{[1
]}

Hou, Jin-Qiang ^{[1
]}

Lu, Yu-Jing ^{[1
]}

Tan, Jia-Heng ^{[1
]}

Gu, Lian-Quan ^{[1
]}

Huang, Zhi-Shu ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 16期

关键词：

9-N-substituted berberine derivatives; synthesis; c-myc G-quadruplex; down-regulation of transcription;

D O I：

10.1016/j.bmc.2008.07.029

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：

A series of 9-N-substituted berberine derivatives (2a-j) were synthesized and evaluated as a new class of G-quadruplex binding ligands. G-quadruplex of DNA had been proven to be the transcription controller of human c-myc gene. The interaction of 9-N-substituted berberine derivatives with G-quadruplex DNA in c-myc was examined via EMSA, CD spectroscopy, FRET-melting method, PCR-stop assay, competitive dialysis, cell proliferation assay and RT-PCR assay. The experiment results indicated that these derivatives could selectively induce and stabilize the formation of intramolecular parallel G-quadruplex in c-myc, which led to down-regulation of transcription of the c-myc in the HL60 lymphomas cell line. The related structure-activity relationships were also discussed. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：7582 / 7591

页数：10

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