Cell-permeable esters of diazeniumdiolate-based nitric oxide prodrugs

Org Lett. 2008 Nov 20;10(22):5155-8. doi: 10.1021/ol8020989. Epub 2008 Oct 29.

Abstract

Although O(2)-(2,4-dinitrophenyl) derivatives of diazeniumdiolate-based nitric oxide (NO) prodrugs bearing a free carboxylic acid group were activated by glutathione to release NO, these compounds were poor sources of intracellular NO and showed diminished antiproliferative activity against human leukemia HL-60 cells. The carboxylic acid esters of these prodrugs, however, were found to be superior sources of intracellular NO and potent inhibitors of HL-60 cell proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Azo Compounds / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Intracellular Space / metabolism
  • Nitric Oxide / chemistry*
  • Nitric Oxide / metabolism*
  • Nitric Oxide / pharmacology
  • Permeability
  • Prodrugs / chemistry*
  • Prodrugs / metabolism*
  • Prodrugs / pharmacology
  • Rats

Substances

  • Azo Compounds
  • Prodrugs
  • diazeniumdiolate
  • Nitric Oxide