1-(2,3-Dibenzimidazol-2-ylpropyl)-2-methoxybenzene Is a Syk Inhibitor with Anti-Inflammatory Properties

Eunji Kim, Young Jin Son, Yanyan Yang, Ting Shen, Ikyon Kim, Adithan Aravinthan, Jong Hoon Kim, Jae Youl Cho

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Inflammation is the protective action of our bodies against external pathogens by recognition of pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). Proper regulation of inflammatory responses is required to maintain our body's homeostasis, as well as there are demands to develop proper acute or chronic inflammation. In this study, we elucidated the regulatory mechanism of NF-κB-mediated inflammatory responses by a novel compound, 1-(2,3-dibenzimidazol-2-ylpropyl)-2-methoxybenzene (DBMB). We found that DBMB suppressed inflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2 ), reacted to exposure to a number of toll like receptor (TLR) ligands. Such observations occurred following to decreased mRNA expression of several pro-inflammatory mediators, and such diminished mRNA levels were caused by inhibited transcriptional factor nuclear factor (NF)-κB, as evaluated by luciferase reporter assay and molecular biological approaches. To find the potential targets of DBMB, we screened phosphorylated forms of NF-κB signal molecules: inhibitor of κBα (IκBα), IκB kinase (IKK)α/β, Akt, 3-phosphoinositide dependent protein kinase-1 (PDK1), p85, and spleen tyrosine kinase (Syk). We found that DBMB treatment could suppress signal transduction through these molecules. Additionally, we conducted in vitro kinase assays using immunoprecipitated Syk and its substrate, p85. Consequently, we could say that DBMB clearly suppressed the kinase activity of Syk kinase activity. Together, our results demonstrate that synthetic DBMB has an effect on the inflammatory NF-κB signaling pathway and suggest the potential for clinical use in the treatment of inflammatory diseases.

Original languageEnglish
Article number508
JournalMolecules
Volume21
Issue number4
DOIs
Publication statusPublished - 2016 Apr

Fingerprint

spleen
tyrosine
Protein-Tyrosine Kinases
inhibitors
Anti-Inflammatory Agents
Phosphotransferases
pathogens
prostaglandins
Assays
3-Phosphoinositide-Dependent Protein Kinases
homeostasis
Inflammation
Pattern Recognition Receptors
nitric oxide
Signal transduction
Messenger RNA
Molecules
pattern recognition
Toll-Like Receptors
Pathogens

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Kim, Eunji ; Son, Young Jin ; Yang, Yanyan ; Shen, Ting ; Kim, Ikyon ; Aravinthan, Adithan ; Kim, Jong Hoon ; Cho, Jae Youl. / 1-(2,3-Dibenzimidazol-2-ylpropyl)-2-methoxybenzene Is a Syk Inhibitor with Anti-Inflammatory Properties. In: Molecules. 2016 ; Vol. 21, No. 4.
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abstract = "Inflammation is the protective action of our bodies against external pathogens by recognition of pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). Proper regulation of inflammatory responses is required to maintain our body's homeostasis, as well as there are demands to develop proper acute or chronic inflammation. In this study, we elucidated the regulatory mechanism of NF-κB-mediated inflammatory responses by a novel compound, 1-(2,3-dibenzimidazol-2-ylpropyl)-2-methoxybenzene (DBMB). We found that DBMB suppressed inflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2 ), reacted to exposure to a number of toll like receptor (TLR) ligands. Such observations occurred following to decreased mRNA expression of several pro-inflammatory mediators, and such diminished mRNA levels were caused by inhibited transcriptional factor nuclear factor (NF)-κB, as evaluated by luciferase reporter assay and molecular biological approaches. To find the potential targets of DBMB, we screened phosphorylated forms of NF-κB signal molecules: inhibitor of κBα (IκBα), IκB kinase (IKK)α/β, Akt, 3-phosphoinositide dependent protein kinase-1 (PDK1), p85, and spleen tyrosine kinase (Syk). We found that DBMB treatment could suppress signal transduction through these molecules. Additionally, we conducted in vitro kinase assays using immunoprecipitated Syk and its substrate, p85. Consequently, we could say that DBMB clearly suppressed the kinase activity of Syk kinase activity. Together, our results demonstrate that synthetic DBMB has an effect on the inflammatory NF-κB signaling pathway and suggest the potential for clinical use in the treatment of inflammatory diseases.",
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1-(2,3-Dibenzimidazol-2-ylpropyl)-2-methoxybenzene Is a Syk Inhibitor with Anti-Inflammatory Properties. / Kim, Eunji; Son, Young Jin; Yang, Yanyan; Shen, Ting; Kim, Ikyon; Aravinthan, Adithan; Kim, Jong Hoon; Cho, Jae Youl.

In: Molecules, Vol. 21, No. 4, 508, 04.2016.

Research output: Contribution to journalArticle

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AU - Son, Young Jin

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AU - Shen, Ting

AU - Kim, Ikyon

AU - Aravinthan, Adithan

AU - Kim, Jong Hoon

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AB - Inflammation is the protective action of our bodies against external pathogens by recognition of pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). Proper regulation of inflammatory responses is required to maintain our body's homeostasis, as well as there are demands to develop proper acute or chronic inflammation. In this study, we elucidated the regulatory mechanism of NF-κB-mediated inflammatory responses by a novel compound, 1-(2,3-dibenzimidazol-2-ylpropyl)-2-methoxybenzene (DBMB). We found that DBMB suppressed inflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2 ), reacted to exposure to a number of toll like receptor (TLR) ligands. Such observations occurred following to decreased mRNA expression of several pro-inflammatory mediators, and such diminished mRNA levels were caused by inhibited transcriptional factor nuclear factor (NF)-κB, as evaluated by luciferase reporter assay and molecular biological approaches. To find the potential targets of DBMB, we screened phosphorylated forms of NF-κB signal molecules: inhibitor of κBα (IκBα), IκB kinase (IKK)α/β, Akt, 3-phosphoinositide dependent protein kinase-1 (PDK1), p85, and spleen tyrosine kinase (Syk). We found that DBMB treatment could suppress signal transduction through these molecules. Additionally, we conducted in vitro kinase assays using immunoprecipitated Syk and its substrate, p85. Consequently, we could say that DBMB clearly suppressed the kinase activity of Syk kinase activity. Together, our results demonstrate that synthetic DBMB has an effect on the inflammatory NF-κB signaling pathway and suggest the potential for clinical use in the treatment of inflammatory diseases.

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