Molecular and biological determinants of the cytotoxic actions of camptothecins. Perspective for the development of new topoisomerase I inhibitors

Ann N Y Acad Sci. 2000;922:11-26. doi: 10.1111/j.1749-6632.2000.tb07021.x.


Camptothecin, originally discovered in 1957 as an antitumor activity in plant extracts, has recently become one of the most promising leads to new anticancer drugs. After lingering for many years, interest in camptothecin was revitalized in 1985 upon discovery of its specific action on topoisomerase I. Detailed elucidation of action mechanisms at the molecular, cellular, and pharmacologic levels has made camptothecin and its congeners perhaps the best understood among clinical anticancer drugs. Promising chemical variants of camptothecin, and recently other chemical categories of topoisomerase I-targeted drugs, provide unusually rich opportunities for rational drug selection and design. This is made possible by current concepts based, for the most part, on a sound experimental foundation, which points the way towards optimally effective therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / toxicity*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / chemistry
  • Camptothecin / toxicity
  • Drug Design
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / toxicity*
  • Humans
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*


  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Topoisomerase I Inhibitors
  • Camptothecin