Synthesis of phenanthridinium-bis-nucleobase conjugates, interactions with poly U, nucleotides and in vitro antitumour activity of mono- and bis-nucleobase conjugates

Eur J Med Chem. 2006 Oct;41(10):1153-66. doi: 10.1016/j.ejmech.2006.05.005. Epub 2006 Jun 21.

Abstract

Novel bis-nucleobase-phenanthridinium conjugates were synthesised and their aqueous solutions spectroscopically characterised. Bis-adenine conjugate revealed in aqueous solutions significantly more pronounced intramolecular aromatic stacking interactions than bis-uracil analogue. In contrast with previously reported poly A recognition by bis-uracil conjugate, recognition of complementary nucleotides and poly U was not observed due to the strong interference of bulk water with hydrogen bonding between nucleobases. The screening of anticancer activity on six human cell lines revealed that tethering of a nucleobase to phenanthridinium moiety diminished antiproliferative potential of phenanthridinium. However, among mono-nucleobase conjugates adenine derivative was found to be the most selective one (MiaPaCa-2, Hep-2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Drug Stability
  • HeLa Cells
  • Humans
  • Hydrogen Bonding
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy / methods
  • Models, Molecular
  • Molecular Structure
  • Nucleotides / chemistry*
  • Phenanthridines / chemistry*
  • Poly U / chemistry*
  • Sensitivity and Specificity
  • Spectrometry, Fluorescence / methods
  • Spectrophotometry, Ultraviolet / methods
  • Structure-Activity Relationship
  • Time Factors

Substances

  • Antineoplastic Agents
  • Nucleotides
  • Phenanthridines
  • phenanthridinium
  • Poly U