Tumor necrosis factor alpha production enhancers with a phenylphthalimide skeleton.
N-2,6-Dialkylphenylphthalimides were found to be strong enhancers of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor necrosis factor (TNF)-alpha production by human leukemia cell line HL-60. Among these compounds, 2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (PP-33) showed the most potent activity (optimum concentration of 10 microM), indicating that the bulkiness of the alkyl groups at the 2 and 6-positions of the phenyl ring moiety is crucial for the activity. Its fluorinated derivative, 2-(2,6-diisopropylphenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3-dio ne (FPP-33) showed the activity at very low concentrations (optimum concentration of 0.1 microM).
Shibata
Y
Y
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Sasaki
K
K
Hashimoto
Y
Y
Iwasaki
S
S
D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology; D010797:Phthalimides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007155:Immunologic Factors; D010797:Phthalimides; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide