Synthesis and pharmacological evaluation of novel non-lactone analogues of camptothecin

Bioorg Med Chem Lett. 2003 Aug 18;13(16):2731-5. doi: 10.1016/s0960-894x(03)00534-1.

Abstract

Ten novel camptothecin (CPT) derivatives devoid of the lactone function in the E-ring were synthesized and evaluated as anticancer agents. Several of these CPT analogues bearing a five-membered E-ring are potent inhibitors of the DNA relaxation and cleavage reactions catalyzed by topoisomerase I and exhibit promising cytotoxic activities with IC(50) values in the nM range. This is the first successful design of lactone-free CPT, providing thus a new avenue to the development of topoisomerase I targeted antitumor agents.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Lactones
  • Topoisomerase I Inhibitors
  • DNA
  • DNA Topoisomerases, Type I
  • Camptothecin