Construction of polyamine-modified uridine and adenosine derivatives--evaluation of DNA binding capacity and cytotoxicity in vitro

Bioorg Med Chem. 2007 Dec 1;15(23):7426-33. doi: 10.1016/j.bmc.2007.07.030. Epub 2007 Aug 21.

Abstract

We here report the synthesis of the two polyamine-based nucleoside derivatives 5-{[bis-(3-aminopropyl)amino]acetamido-1-propynyl}uridine and 2-{[bis-(3-aminopropyl)amino]-acetamido-1-propynyl}adenosine. The various polyamine derivatives have been used in thermal melting analysis using DNA from herring testes, and in cellular studies using four different cell lines. The compounds were all found to be non-toxic, thus holding good promise for future use as siRNA building blocks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis*
  • Adenosine / pharmacology*
  • Binding Sites
  • Breast Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Circular Dichroism / methods
  • DNA / chemistry
  • DNA / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • In Vitro Techniques
  • Molecular Structure
  • Polyamines / chemistry*
  • Structure-Activity Relationship
  • Temperature
  • Tumor Cells, Cultured
  • Uridine / analogs & derivatives*
  • Uridine / chemical synthesis*
  • Uridine / pharmacology*

Substances

  • 5-((bis-(3-aminopropyl)amino)acetamido-1-propynyl)adenosine
  • 5-((bis-(3-aminopropyl)amino)acetamido-1-propynyl)uridine
  • Polyamines
  • DNA
  • Adenosine
  • Uridine