Bisorbicillinol inhibits Lyn tyrosine kinase for allergic response on RBL-2H3 cells

Kouichi Sugaya; Takehito Terajima; Aika Takahashi; Jun-Ichi Onose; Naoki Abe

doi:10.1016/j.bmcl.2019.01.019

Bisorbicillinol inhibits Lyn tyrosine kinase for allergic response on RBL-2H3 cells

Bioorg Med Chem Lett. 2019 Mar 15;29(6):832-835. doi: 10.1016/j.bmcl.2019.01.019. Epub 2019 Jan 19.

Authors

Kouichi Sugaya¹, Takehito Terajima¹, Aika Takahashi¹, Jun-Ichi Onose², Naoki Abe³

Affiliations

¹ Department of Nutritional Science and Food Safety, Faculty of Applied Bio-Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
² Department of Nutritional Science and Food Safety, Faculty of Applied Bio-Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan. Electronic address: j1onose@nodai.ac.jp.
³ Department of Nutritional Science and Food Safety, Faculty of Applied Bio-Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan. Electronic address: abe@nodai.ac.jp.

PMID: 30711393
DOI: 10.1016/j.bmcl.2019.01.019

Abstract

Bisorbicillinol, which is isolated from Trichoderma sp. USF2690, is an inhibitor of β-hexosaminidase release and tumor necrosis factor (TNF)-α, and Interleukin (IL)-4 secretion from rat basophilic leukemia (RBL-2H3) cells, with IC₅₀ values of 2.8 μM, 2.9 μM and 2.8 μM respectively. We showed that the inhibitory mechanism of β-hexosaminidase release and TNF-α secretion involved inhibition of Lyn, a tyrosine kinase. The inhibitory activities of bisorbicillinol indicate that this compound is a new candidate anti-allergic agent.

Keywords: Bisorbicillinol; Lyn; RBL-2H3 cells; TNF-α; β-Hexosaminidase.

MeSH terms

Animals
Anti-Allergic Agents / pharmacology*
Bridged-Ring Compounds / pharmacology*
Cell Degranulation / drug effects
Cell Line, Tumor
Mast Cells / drug effects
Protein Kinase Inhibitors / pharmacology*
Rats
Receptors, IgE / metabolism
Signal Transduction / drug effects
Tumor Necrosis Factor-alpha / antagonists & inhibitors
beta-N-Acetylhexosaminidases / antagonists & inhibitors
src-Family Kinases / antagonists & inhibitors*

Substances

Anti-Allergic Agents
Bridged-Ring Compounds
Protein Kinase Inhibitors
Receptors, IgE
Tumor Necrosis Factor-alpha
bisorbicillinol
lyn protein-tyrosine kinase
src-Family Kinases
beta-N-Acetylhexosaminidases