Novel biological response modifiers: phthalimides with tumor necrosis factor-alpha production-regulating activity

J Med Chem. 1997 Aug 29;40(18):2858-65. doi: 10.1021/jm970109q.

Abstract

Novel N-substituted phthalimides (2-substituted 1H-isoindole-1,3-diones) were prepared, and their effects on tumor necrosis factor-alpha (TNF-alpha) production by human leukemia cell line HL-60 stimulated with 12-O-tetradecanoylphorbol 13-acetate (TPA) or okadaic acid (OA) were examined. A structure-activity relationship study of the N-phenylphthalimides and N-benzylphthalimides revealed that their enhancing effect on TPA-induced TNF-alpha production by HL-60 cells and their inhibiting effect on OA-induced TNF-alpha production by HL-60 cells are only partially correlated.

Publication types

  • Comparative Study

MeSH terms

  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • HL-60 Cells / drug effects*
  • HL-60 Cells / physiology
  • Humans
  • Immunologic Factors / chemical synthesis
  • Immunologic Factors / chemistry*
  • Immunologic Factors / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Okadaic Acid / pharmacology
  • Optical Rotation
  • Phthalimides / chemical synthesis
  • Phthalimides / chemistry*
  • Phthalimides / pharmacology*
  • Structure-Activity Relationship
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Immunologic Factors
  • Phthalimides
  • Tumor Necrosis Factor-alpha
  • Okadaic Acid
  • Tetradecanoylphorbol Acetate