Tumor necrosis factor-alpha production-inhibiting activity of phthalimide analogues on human leukemia THP-1 cells and a structure-activity relationship study.
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.
Miyachi
H
H
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Ogasawara
A
A
Azuma
A
A
Hashimoto
Y
Y
D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010797:Phthalimides / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D010797:Phthalimides; D014409:Tumor Necrosis Factor-alpha; D019319:Okadaic Acid; D013755:Tetradecanoylphorbol Acetate