title: 2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide as a new lead compound for management of allergic rhinitis.
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.
authors: Department of Pharmacology, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors: Hee-Yun
authors: HY
authors: Kim
authors: Department of Pharmacology, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors: Sun-Young
authors: SY
authors: Nam
authors: Department of Pharmaceutical Engineering and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam, 31499, Republic of Korea.
authors: Jae-Bum
authors: JB
authors: Jang
authors: 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.
authors: Youngjin
authors: Y
authors: Choi
authors: Biochip Research Center and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam, 31499, Republic of Korea.
authors: In-Cheol
authors: IC
authors: Kang
authors: Department of Pharmacology, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea. hmkim@khu.ac.kr.
authors: Hyung-Min
authors: HM
authors: Kim
authors: 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. hjjeong@hoseo.edu.
authors: Hyun-Ja
authors: HJ
authors: Jeong
mesh_terms: D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use*; D000485:Allergens; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000097:blood; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use*; D007073:Immunoglobulin E / Q000097:blood; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D010047:Ovalbumin; D065631:Rhinitis, Allergic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
chemical_list: C000616812:2-(4-(2-((phenylthio)acetyl)carbonohydrazonoyl)phenoxy)acetamide; D000081:Acetamides; D000485:Allergens; D018926:Anti-Allergic Agents; D016207:Cytokines; D006835:Hydrazones; D007073:Immunoglobulin E; D006632:Histamine; D010047:Ovalbumin; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020170:Caspase 1
keywords: 2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide; Allergic rhinitis; Caspase-1; Molecular docking simulation; TSLP