Membrane-permeant, bioactivatable analogues of cGMP as inducers of cell death in IPC-81 leukemia cells

Bioorg Med Chem Lett. 2000 Mar 20;10(6):571-3. doi: 10.1016/s0960-894x(00)00050-0.

Abstract

We report an improved single-step synthesis to generate the membrane-permeant acetoxymethyl esters (AM-esters) of cGMP and three cGMP-analogues. These bioactivatable compounds were found to induce cell death in rat IPC-81 cells, a model system for acute myelocytic leukemia, in micromolar doses, while the corresponding non-modified cGMP-analogues were inactive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Biotransformation
  • Cell Death / drug effects
  • Cell Line
  • Cell Membrane Permeability / drug effects
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / chemical synthesis
  • Cyclic GMP / pharmacology
  • Humans
  • Leukemia, Experimental / drug therapy*
  • Leukemia, Myeloid, Acute / drug therapy
  • Rats
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • 8-bromocyclic GMP
  • Cyclic GMP