Effects of Bifunctional Netropsin-Related Minor Groove-Binding Ligands on Mammalian Type I DNA Topoisomerase

Biochem Pharmacol. 1997 Feb 7;53(3):309-16. doi: 10.1016/s0006-2952(96)00690-9.


We investigated the effects of compounds with two covalently linked netropsin moieties (bis-netropsin) on the function of mammalian type I DNA topoisomerase (topo I) in vitro. We initiated these studies because earlier studies had shown that certain bis-netropsins possess a several-fold higher antitumor and antiviral activity than netropsin. We confirmed that the parent compound netropsin, but not its bifunctional derivatives, induce supercoils in closed DNA. We determined that bis-netropsins inhibit the binding of topo I to DNA more efficiently than netropsin and that bis-netropsins but not netropsin induce specific DNA strand cleavage in the presence of topo I. We discuss a model explaining the different effects of netropsin and bis-netropsins on topo I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Base Sequence
  • DNA / metabolism
  • DNA Damage
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Netropsin / analogs & derivatives*
  • Netropsin / pharmacology
  • Topoisomerase I Inhibitors*


  • Antineoplastic Agents
  • Topoisomerase I Inhibitors
  • Netropsin
  • bis-netropsin
  • DNA