Phenylphthalimides with Tumor Necrosis Factor Alpha Production-Enhancing Activity

• SHIBATA Yoshihiro

  Institute of Molecular and Cellular Biosciences, The University of Tokyo

• SASAKI Keizo

  Institute of Molecular and Cellular Biosciences, The University of Tokyo

• HASHIMOTO Yuichi

  Institute of Molecular and Cellular Biosciences, The University of Tokyo

• IWASAKI Shigeo

  Institute of Molecular and Cellular Biosciences, The University of Tokyo

抄録

Phenylphthalimides (2-phenyl-1H-isoindole-1,3-diones) were prepared and their effects on tumor necrosis factor alpha (TNF-α) production by human leukemia cell line HL-60 stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined. An analysis of the structure-activity relationships of the phenylphthalimides indicated that potent enhancing activity on TPA-induced TNF-α production by HL-60 cells requires medium-sized substituent(s) at the ortho position(s) of the phenyl group; 2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (PP-33) increased the TNF-α production to more than 600% at the concentration of 1×10^<-5> M. Introduction of a nitro group at the phthalimide moiety of PP-33 enhanced the activity; 2-(2,6-diisopropylphenyl)-4-nitro-1H-isoindole-1,3-dione (4NPP-33) and its 5-nitro isomer (5NPP-33) enhanced the TNF-α production to more than 800% and 700%, respectively, at the concentration of 1×10^<-5> M. Introduction of fluorines into the phthalimide moiety of PP-33 greatly lowered the concentration of the compound necessary to elicit the TNF-α production-enhancing activity;2-(2,6-diisopropylphenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3-dione (FPP-33) showed the activity at nanomolar concentration, with the optimum concentration of 1×10^<-7> M.

収録刊行物

• Chemical & pharmaceutical bulletin

  Chemical & pharmaceutical bulletin 44 (1), 156-162, 1996-01-15

  公益社団法人日本薬学会

キーワード

• tumor necrosis factor alpha
• phenylphthalimide
• structure-activity relationship

詳細情報

• CRID: 1573105977186204800
• NII論文ID: 110003631737
• NII書誌ID: AA00602100
• ISSN: 00092363
• 本文言語コード: en
• データソース種別:
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