Design, synthesis, and evaluation of DNA topoisomerase II-targeted nucleosides

Bioorg Med Chem. 2017 Aug 1;25(15):4133-4144. doi: 10.1016/j.bmc.2017.06.001. Epub 2017 Jun 2.

Abstract

We developed novel nucleoside-based topoisomerase II selective inhibitors and showed that small structural units, such as catechols, are essential for DNA topoisomerase II inhibitory activity. Moreover, nucleoside analogues containing TBS and 1,3-dithian moieties had potent and selective DNA topoisomerase II inhibitory activities. In further experiments, compound 25b having a beta configuration of the thymine moiety showed relatively strong growth inhibitory activity against cancer cell lines, and was more potent against all cancer cell lines than compound 26b, which carries a thymine moiety in the alpha configuration.

Keywords: Antiproliferative activity; Cancer; DNA topoisomerase; Nucleoside.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon-13 Magnetic Resonance Spectroscopy
  • Cell Line, Tumor
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Mass Spectrometry
  • Nucleotides / antagonists & inhibitors*
  • Proton Magnetic Resonance Spectroscopy
  • Spectrophotometry, Infrared
  • Topoisomerase II Inhibitors / chemistry
  • Topoisomerase II Inhibitors / pharmacology*

Substances

  • Nucleotides
  • Topoisomerase II Inhibitors