Chika Shimada

Keio University, Edo, Tōkyō, Japan

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Publications (2)3.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The amino-epoxyquinols 6a and 6b were synthesized as soluble derivatives of an NF-κB inhibitor DHMEQ (1). In spite of the opposite configuration from 1, 6b rather than 6a affected the deactivation of NF-κB, based on NO secretion and MALDI-TOF MS analysis. It was indicated that 6b inhibited the activation by different manner from that of 1.
    No preview · Article · Oct 2010 · Bioorganic & medicinal chemistry letters
  • Chika Shimada · Yoko Ninomiya · Eriko Suzuki · Kazuo Umezawa
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    ABSTRACT: NF-kappaB is a transcription factor that induces the expression of inflammatory cytokines and antiapoptotic proteins. Earlier we designed a new NF-kappaB inhibitor, (-)-DHMEQ, and showed that it had potent anticancer and anti-inflammatory activities in various animal models without any toxicity. In the present research, we studied whether (-)-DHMEQ could be efficiently taken by cultured cells and irreversibly inhibit NF-kappaB by short time application to cultured cells. Even after mouse monocytic leukaemia RAW264.7 cells had been washed free of (-)-DHMEQ, lipopolysacharide (LPS)-induced activation of NF-kappaB in these cells was still inhibited. Moreover, topical application for 15 min was found to induce dormancy of the cells against LPS for 2-8 h. When it was topically added to RAW264.7 cells in which NF-kappaB was activated by LPS, the inhibition lasted at least for 2 h. NF-kappaB derectly upregulates expression of iNOS that produces NO. Short time application of (-)-DHMEQ also inhibited the function of cells in terms of NO production and iNOS induction in RAW264.7 cells. Thus, the fast incorporation of (-)-DHMEQ into the cells and irreversible inhibition of NF-kappaB by it were demonstrated, and this observation would explain its effective inhibition of certain functions in cellular and animal disease models.
    No preview · Article · Jan 2010 · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics