Inhibitory activities against topoisomerase I and II by polyhydroxybenzoyl amide derivatives and their structure-activity relationship

Bioorg Med Chem Lett. 2004 Apr 5;14(7):1669-72. doi: 10.1016/j.bmcl.2004.01.060.

Abstract

o-, m-, p-Phenylenediamines having 2,3,4-trihydroxy, 3,4 dihydroxy, and 4-hydroxybenzoyl moieties were prepared and their inhibitory activities were measured against topoisomerase I and II. More hydroxy groups on two aromatic rings increased the activities. Bis(trihydroxybenzoyl)-o-phenylenediamide showed IC(50)=0.90 and 0.09 microM against topoisomerase I and II, respectively. Compounds with hydroxy groups protected by acetyl moiety still had the activities. Less hydroxy groups decreased their activities. Benzothiazole derivatives also indicated the activities.

MeSH terms

  • Cell Cycle / drug effects
  • DNA Topoisomerases, Type I / metabolism
  • DNA Topoisomerases, Type II / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Growth Inhibitors / chemistry
  • Growth Inhibitors / pharmacology
  • HeLa Cells
  • Humans
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*
  • Topoisomerase II Inhibitors*

Substances

  • Enzyme Inhibitors
  • Growth Inhibitors
  • Topoisomerase I Inhibitors
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type I
  • DNA Topoisomerases, Type II