DNA polymerases and DNA topoisomerases as targets for the development of anticancer drugs

Anticancer Res. Sep-Oct 1986;6(5):935-40.


Studies of a variety of compounds designed as derivatives of prototype active molecules aphidicolin and doxorubicin are reported. So far none of the aphidicolin simpler analogues is as active as the parental molecule. Ten anthracycline analogues, characterized for their cytotoxicity, antitumor activity and inhibition of the relaxing activity of purified human DNA topoisomerase II can be divided into five groups. The majority of the tested compounds shows properties very similar to those of doxorubicin. Epirubicin shows extremely high inhibitory activity toward the relaxing property of topoisomerase II but its antitumor activity and cytotoxicity are similar to those of the former group. The third group includes a compound with extremely high cytotoxicity. The fourth group is represented by a compound which shows a cytotoxicity. The fourth group is represented by a compound which shows a cytotoxicity. The fourth group is represented by a compound which shows a cytotoxicity typical of anthracyclines and good antitumor activity but which has no specific inhibitory activity on topoisomerase II. A fifth group includes a totally inactive compound. Our results suggest that the inhibition of human DNA topoisomerase II is only partially correlated with antitumor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / therapeutic use
  • Aphidicolin
  • Cell Line
  • Cell Survival / drug effects
  • DNA Polymerase II / antagonists & inhibitors
  • DNA Replication
  • Daunorubicin / analogs & derivatives
  • Daunorubicin / therapeutic use
  • Diterpenes / therapeutic use*
  • Doxorubicin / analogs & derivatives
  • Doxorubicin / therapeutic use
  • Epirubicin
  • Humans
  • Idarubicin
  • In Vitro Techniques
  • Melanoma / drug therapy
  • Nucleic Acid Synthesis Inhibitors*
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*


  • Antineoplastic Agents
  • Diterpenes
  • Nucleic Acid Synthesis Inhibitors
  • Topoisomerase I Inhibitors
  • Aphidicolin
  • Epirubicin
  • Doxorubicin
  • DNA Polymerase II
  • esorubicin
  • Idarubicin
  • Daunorubicin