Synthesis and evaluation of 9-O-substituted berberine derivatives containing aza-aromatic terminal group as highly selective telomeric G-quadruplex stabilizing ligands

Bioorg Med Chem Lett. 2009 Jul 1;19(13):3414-7. doi: 10.1016/j.bmcl.2009.05.030. Epub 2009 May 14.

Abstract

A series of new 9-O-substituted berberine derivatives (4a-j) as telomeric quadruplex ligands was synthesized and evaluated. The results from biophysical and biochemical assay indicated that introducing of positive charged aza-aromatic terminal group into the side chain of 9-position of berberine significantly improved the binding ability with G-quadruplex, and exhibited the inhibitory effect on the hybridization and on telomerase activity. These derivatives showed excellent selectivity for telomeric G-quadruplex DNA over duplex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aza Compounds / chemistry*
  • Berberine / analogs & derivatives*
  • Berberine / chemical synthesis
  • Berberine / pharmacology
  • Cell Line, Tumor
  • Fluorescence Resonance Energy Transfer
  • G-Quadruplexes*
  • Humans
  • Ligands
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Telomerase / antagonists & inhibitors*
  • Telomerase / metabolism
  • Telomere / chemistry*

Substances

  • Aza Compounds
  • Ligands
  • Reverse Transcriptase Inhibitors
  • Berberine
  • Telomerase