DNA Topoisomerases and Their Poisoning by Anticancer and Antibacterial Drugs

Chem Biol. 2010 May 28;17(5):421-33. doi: 10.1016/j.chembiol.2010.04.012.

Abstract

DNA topoisomerases are the targets of important anticancer and antibacterial drugs. Camptothecins and novel noncamptothecins in clinical development (indenoisoquinolines and ARC-111) target eukaryotic type IB topoisomerases (Top1), whereas human type IIA topoisomerases (Top2alpha and Top2beta) are the targets of the widely used anticancer agents etoposide, anthracyclines (doxorubicin, daunorubicin), and mitoxantrone. Bacterial type II topoisomerases (gyrase and Topo IV) are the targets of quinolones and aminocoumarin antibiotics. This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors. We also discuss the common mechanism of action of topoisomerase poisons by interfacial inhibition and trapping of topoisomerase cleavage complexes.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Camptothecin / chemistry
  • Camptothecin / pharmacology
  • DNA Topoisomerases / metabolism
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Etoposide / chemistry
  • Etoposide / pharmacology
  • Humans
  • Mitoxantrone / chemistry
  • Mitoxantrone / pharmacology
  • Quinolones / chemistry
  • Quinolones / pharmacology
  • Topoisomerase Inhibitors*

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Quinolones
  • Topoisomerase Inhibitors
  • Etoposide
  • Doxorubicin
  • Mitoxantrone
  • DNA Topoisomerases
  • Camptothecin