Topoisomerase II Inhibitors: Prospects for New Antifungal Agents

  • David E. Jackson
  • D. P. Figgitt
  • Stephen P. Denyer


The DNA of both prokaryotic and eukaryotic cells exhibits several common tertiary structures including supercoils, knots, and catenanes, each of which is involved in various cellular processes (101, 80, 99). These topological forms of DNA may arise as a result of it being in a closed, circular form (rings or loops) such as in plasmid, viral, phage, or bacterial genomic DNA. Alternatively, the genomic DNA of eukaryotes may be complexed with proteins and other cellular molecules, at two points or more, in such a way that the ends are restricted and not free to rotate. Such constrained DNA domains (80, 103) pose certain topological problems that must be resolved by the cellular apparatus for successful propagation of the genetic material. This is achieved in both prokaryotic and eukaryotic organisms by a family of enzymes referred to as DNA topoisomerases. The enzymes are subdivided into type I and type II based on their ability to catalyse single- or double-strand cleavages, respectively; in addition type II enzymes have an energy requirement satisfied by ATP. In bacteria, topoisomerase II is often referred to as bacterial gyrase. E. coli contains two type I topoisomerases, the TopA and TopB proteins (84, 87).


Cleavage Complex Podophyllum Hexandrum Antifungal Antibiotic Antitumour Drug Eukaryotic Type 
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Copyright information

© Springer Science+Business Media Dordrecht 1992

Authors and Affiliations

  • David E. Jackson
  • D. P. Figgitt
  • Stephen P. Denyer

There are no affiliations available

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