Molecular Recognition and Imaging of Human Telomeric G-Quadruplex DNA in Live Cells: A Systematic Advancement of Thiazole Orange Scaffold to Enhance Binding Specificity and Inhibition of Gene Expression

Wei Long, Bo Xin Zheng, Xuan He Huang, Meng Ting She, Ao Lu Liu, Kun Zhang, Wing Leung Wong (Corresponding Author), Yu Jing Lu

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7 Citations (Scopus)


A series of fluorescent ligands, which were systematically constructed from thiazole orange scaffold, was investigated for their interactions with G-quadruplex structures and antitumor activity. Among the ligands, compound 3 was identified to exhibit excellent specificity toward telomere G4-DNA over other nucleic acids. The affinity of 3-Htg24 was almost 5 times higher than that of double-stranded DNA and promoter G4-DNA. Interaction studies showed that 3 may bind to both G-tetrad and the lateral loop near the 5′-end. The intracellular colocalization with BG4 and competition studies with BRACO19 reveal that 3 may interact with G4-structures. Moreover, 3 reduces the telomere length and downregulates hTERC and hTERT mRNA expression in HeLa cells. The cytotoxicity of 3 against cancer cells (IC50 = 12.7-16.2 μM) was found to be generally higher than noncancer cells (IC50 = 52.3 μM). The findings may support that the ligand is telomere G4-DNA specific and may provide meaningful insights for anticancer drug design.

Original languageEnglish
Pages (from-to)2125-2138
Number of pages14
JournalJournal of Medicinal Chemistry
Issue number4
Publication statusPublished - 25 Feb 2021

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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