Stabilization of G-quadruplex DNA and down-regulation of oncogene c-myc by quindoline derivatives

Tian Miao Ou, Yu Jing Lu, Chi Zhang, Zhi Shu Huang*, Xiao Dong Wang, Jia Heng Tan, Yuan Chen, Dik Lung Ma, Kwok Yin Wong, Johnny Cheuk On Tang, Albert Sun Chi Chan, Lian Quan Gu

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

272 Citations (Scopus)


Stabilization of G-quadruplex structures in the promoter region of certain oncogenes is an emerging field in anticancer drug design. Human c-myc gene is one of these oncogenes, and G-quadruplexes have been proven to be the transcriptional controller of this gene. In the present study, the interaction of quindoline derivatives with G-quadruplexes in c-myc was investigated. The experimental results indicated that these derivatives have the ability to induce/stabilize the G-quadruplexes in c-myc, which lead to down-regulation of the c-myc in the Hep G2 cell line. It was found that derivatives with terminal amino groups in their side chains would selectively bind to the isomers with the double nucleotide loops in the absence of K+. Molecular modeling studies revealed the binding mode between the derivatives and the G-quadruplexes is end-stacking at the 3‘-position, and the positively charged side chain on the quindoline derivatives may contribute to the selectivity to certain loop isomers of topological quadruplexes as well as the improved stabilization action.

Original languageEnglish
Pages (from-to)1465-1474
Number of pages10
JournalJournal of Medicinal Chemistry
Issue number7
Publication statusPublished - 5 Apr 2007

Scopus Subject Areas

  • Molecular Medicine
  • Drug Discovery


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