Camptothecin: current perspectives

Bioorg Med Chem. 2004 Apr 1;12(7):1585-604. doi: 10.1016/j.bmc.2003.11.036.


This review provides a detailed discussion of recent advances in the medicinal chemistry of camptothecin, a potent antitumor antibiotic. Two camptothecin analogues are presently approved for use in the clinic as antitumor agents and several others are in clinical trials. Camptothecin possesses a novel mechanism of action involving the inhibition of DNA relaxation by DNA topoisomerase I, and more specifically the stabilization of a covalent binary complex formed between topoisomerase I and DNA. This review summarizes the current status of studies of the mechanism of action of camptothecin, including topoisomerase I inhibition and additional cellular responses. Modern synthetic approaches to camptothecin and several of the semi-synthetic methods are also discussed. Finally, a systematic evaluation of novel and important analogues of camptothecin and their contribution to the current structure-activity profile are considered.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / pharmacology
  • Camptothecin* / analogs & derivatives
  • Camptothecin* / chemical synthesis
  • Camptothecin* / pharmacology
  • Cell Division / drug effects
  • Cell Line, Tumor
  • DNA / chemistry
  • DNA / drug effects
  • DNA / metabolism
  • DNA Topoisomerases, Type I / metabolism
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors


  • Antineoplastic Agents
  • Topoisomerase I Inhibitors
  • DNA
  • DNA Topoisomerases, Type I
  • Camptothecin