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2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide as a new lead compound for management of allergic rhinitis

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Abstract

Objective

We selected a hit compound, 2-(4-{2-[(phenylthio)acetyl]-carbonohydrazonoyl}-phenoxy)acetamide (PA), by a molecular docking simulation between 636,565 compounds and caspase-1 protein. We examined the effect of PA on allergic rhinitis (AR) animal model.

Methods

We assessed the therapeutic effects and the regulatory mechanisms of ovalbumin (OVA)-sensitized mouse model of AR.

Results

A molecular docking simulation and a kinetic assay indicated that PA regulates the caspase-1 activation through the interaction with the caspase-1 active site. In the AR animal model, PA significantly reduced the rub scoring increased by OVA. The up-regulated IgE, histamine, interleukin (IL)-1β, and thymic stromal lymphopoietin (TSLP) levels in the serum of OVA-sensitized mice were significantly decreased by the treatment with PA. Protein levels of IL-1β, IL-5, IL-6, IL-13, tumor necrosis factor-α, TSLP, cyclooxygenase-2, macrophage inflammatory protein-2, and intercellular adhesion molecule-1 were also significantly inhibited by the treatment with PA in the nasal mucosa tissues of the OVA-sensitized mice. In the PA-treated mice, the number of eosinophils and mast cells infiltrated by OVA-sensitization were also reduced. In addition, PA reduced the mast cell-derived caspase-1 activity and expression in the nasal mucosa tissues of the OVA-sensitized mice.

Conclusions

PA showed the possibility to regulate AR in OVA-induced AR models, suggesting that it has therapeutic potential for the management of AR as a lead compound.

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Acknowledgments

This research was supported by the Academic Research fund of Hoseo University in 2015 (2015-0228).

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Authors and Affiliations

  1. Department of Pharmacology, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea

    Hee-Yun Kim, Sun-Young Nam & Hyung-Min Kim

  2. Department of Pharmaceutical Engineering and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam, 31499, Republic of Korea

    Jae-Bum Jang

  3. Department of Food Technology and Inflammatory Disease Research Center, Hoseo University, 20 Hoseo-ro, 79 Beon-gil, Baebang-eup, Asan, Chungnam, 31499, Republic of Korea

    Youngjin Choi & Hyun-Ja Jeong

  4. Biochip Research Center and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam, 31499, Republic of Korea

    In-Cheol Kang

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  1. Hee-Yun Kim
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Correspondence to Hyung-Min Kim or Hyun-Ja Jeong.

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Kim, HY., Nam, SY., Jang, JB. et al. 2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide as a new lead compound for management of allergic rhinitis. Inflamm. Res. 65, 963–973 (2016). https://doi.org/10.1007/s00011-016-0979-1

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  • DOI: https://doi.org/10.1007/s00011-016-0979-1

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