Enantioselective synthesis and biological activity of (3S,4R)- and (3S,4S)-3-hydroxy-4-hydroxymethyl- 4-butanolides in relation to PGE2

J Med Chem. 2004 Jan 15;47(2):292-5. doi: 10.1021/jm034216y.

Abstract

Compounds 9 and 13 were synthesized, and their structures and stereochemistry were elucidated by spectroscopic methods. In competition binding experiments, specific [(3)H]-PGE(2) binding was significantly displaced by compound 9 and, to a lesser extent, by 13, in a dose-dependent manner. The biological properties of compound 9 were studied on HL-60 cells, and several effects were found related to those of PGE(2). Compound 9 increases c-fos mRNA level as does PGE(2) and antagonizes TPA-induced terminal differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis*
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / pharmacology
  • Binding, Competitive
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Dinoprostone / chemistry
  • Dinoprostone / metabolism*
  • HL-60 Cells
  • Humans
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / genetics
  • RNA, Messenger / biosynthesis
  • Radioligand Assay
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Dinoprostone
  • Tetradecanoylphorbol Acetate
  • 4-Butyrolactone