Carbazole ligands as c-myc G-quadruplex binders

Int J Biol Macromol. 2018 Jul 15;114:479-490. doi: 10.1016/j.ijbiomac.2018.03.135. Epub 2018 Mar 23.

Abstract

The interactions of c-myc G-quadruplex with three carbazole derivatives were investigated by UV-Vis spectrophotometry, fluorescence, CD spectroscopy, and molecular modeling. The results showed that a combination of carbazole scaffold functionalized with ethyl, triazole and imidazole groups resulted in stabilization of the intramolecular G-quadruplex formed by the DNA sequence derived from the NHE III1 region of c-myc oncogene (Pu22). Binding to the G-quadruplex Pu22 resulted in the significant increase in fluorescence intensity of complexed ligands 1-3. All ligands were capable of interacting with G4 DNA with binding stoichiometry indicating that two ligand molecules bind to G-quadruplex with comparable affinity, which agrees with binding model of end-stacking on terminal G-tetrads.

Keywords: Carbazole derivatives; Molecular modeling; Pu22; Spectroscopy; c-myc G-quadruplex.

MeSH terms

  • Carbazoles / chemistry*
  • G-Quadruplexes*
  • Genes, myc*
  • Humans
  • Ligands

Substances

  • Carbazoles
  • Ligands