Structure-based design of flavone derivatives as c-myc oncogene down-regulators

Hui Yang, Hai Jing Zhong, Ka Ho Leung, Daniel Shiu Hin Chan, Victor Pui Yan Ma, Wai Chung Fu, Rupesh Nanjunda, W. David Wilson, Edmond Dik Lung MA*, Chung Hang Leung

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

22 Citations (Scopus)


Based on molecular docking analysis of complexes between flavone and the c-myc G-quadruplex, we designed and screened 30 flavone derivatives containing various side chains that could potentially form interactions with the G-quadruplex grooves. As a proof-of-concept, the highest-scoring flavone derivatives containing cationic pyridinium side chains were synthesized and their interactions with the c-myc G-quadruplex were examined using a PCR-stop assay. The stabilizing effects of the flavone derivatives were found to be selective towards the c-myc G-quadruplex over other biologically relevant G-quadruplex structures, such as the human telomeric sequence (HTS). The interaction between the most potent compound of the series and the c-myc G-quadruplex was examined in depth using UV-Vis titration, molecular modeling and CD spectroscopy. Our results suggest that in addition to stabilizing the c-myc G-quadruplex, the flavone derivatives were capable of inducing the formation of the G-quadruplex structure even in the absence of monovalent cations. The flavone derivatives were found to be potent inhibitors of c-myc promoters within the cellular environment and displayed promising cytotoxic behavior against human cancer cell lines.

Original languageEnglish
Pages (from-to)130-141
Number of pages12
JournalEuropean Journal of Pharmaceutical Sciences
Issue number1-2
Publication statusPublished - 23 Jan 2013

Scopus Subject Areas

  • Pharmaceutical Science

User-Defined Keywords

  • c-myc
  • Flavone derivatives
  • G-quadruplex DNA
  • Structure-based design


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