Synthesis of novel water-soluble 7-(aminoacylhydrazono)-formyl camptothecins with potent inhibition of DNA topoisomerase I

Bioorg Med Chem. 1994 Dec;2(12):1397-402. doi: 10.1016/s0968-0896(00)82091-x.

Abstract

Eighteen new water-soluble 7-(aminoacylhydrazono)-formyl camptothecins were synthesized and evaluated for their ability to cause protein-linked DNA breaks and to inhibit topoisomerase I activity. Compared with camptothecin, five of the compounds were as potent or more potent in these tw assays but were less toxic in several cancer cell lines. The results suggest that the 7 position in the B ring is a suitable location for introducing a polar moiety into camptothecin producing analogues with enhanced topoisomerase I inhibiting activity.

Publication types

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

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Camptothecin / analogs & derivatives*
  • Camptothecin / chemistry
  • Camptothecin / pharmacology
  • Cell Division / drug effects
  • DNA Damage
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • KB Cells
  • Mass Spectrometry
  • Molecular Structure
  • Solubility
  • Spectrophotometry, Infrared
  • Topoisomerase I Inhibitors*

Substances

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