Tumor necrosis factor-alpha production-inhibiting activity of phthalimide analogues on human leukemia THP-1 cells and a structure-activity relationship study.

Abstract

N-Substituted phthalimides (2-substituted 1H-isoindole-1,3-diones) were prepared and their inhibitory effects on tumor necrosis factor-alpha (TNF-alpha) production by human leukemia cell line THP-1 stimulated with 12-O-tetradecanoylphorbol 13-acetate (TPA) or okadaic acid (OA) were examined. A structure-activity relationship study of these phthalimide analogues revealed that their inhibitory effects on TPA- and OA-induced TNF-alpha production by THP-1 cells are well correlated to each other, i.e. they may involve the same target molecule(s). An analysis by the use of phthalimide analogue-immobilized affinity gels indicated the existence of several phthalimide-binding proteins in THP-1 cell extract.

• Authors: H Miyachi, A Ogasawara, A Azuma, Y Hashimoto
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 5 Issue 11 Pg. 2095-102 (Nov 1997) ISSN: 0968-0896 [Print] England
• PMID: 9416426 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Drug Screening Assays, Antitumor
• Humans
• Leukemia, Monocytic, Acute (metabolism)
• Okadaic Acid (pharmacology)
• Phthalimides (chemical synthesis, pharmacology)
• Structure-Activity Relationship
• Tetradecanoylphorbol Acetate (pharmacology)
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, biosynthesis)