Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives

Mohd Fadhlizil Fasihi Mohd Aluwi, Kamal Rullah, Md Areeful Haque, Bohari Mohd. Yamin, Waqas Ahmad, Muhammad Wahab Amjad, Sze Wei Leong, Nurul Amira Fahmizar, Juriyati Jalil, Faridah Abas, Nor Hadiani Ismail, Ibrahim Jantan, Kok Wai Lam

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Curcumin is an important molecule found in turmeric plants and has been reported to exhibit some profound anti-inflammatory activities by interacting with several important molecular targets found in the mitogen-activated protein kinase and NF-κβ pathways. As part of our continuing effort to search for new anti-inflammatory agents with better in vitro and in vivo efficacies, we have synthesized a series of new unsymmetrical dicarbonyl curcumin derivatives and tested their effects on prostaglandin E2 secretion level in interferon-γ/lipopolysaccharide-activated macrophage cells. Among those, five compounds exhibited remarkable suppression on prostaglandin E2 production with IC50 values ranging from 0.87 to 18.41 µM. The most potent compound 17f was found to down-regulate the expression of cyclooxygenase-2 mRNA suggesting that this series of compounds could possibly target the mitogen-activated protein kinase signal transduction pathway. Whilst the compound did not affect the expression of the conventional mitogen-activated protein kinases, the results suggest that it could disrupt the phosphorylation and activation of the proteins particularly the c-Jun N-terminal kinases. Finally, the binding interactions were examined using the molecular docking and dynamics simulation approaches.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalMedicinal Chemistry Research
DOIs
Publication statusAccepted/In press - 18 Aug 2017

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Phosphorylation
Curcumin
Mitogen-Activated Protein Kinases
Dinoprostone
Derivatives
Anti-Inflammatory Agents
Molecular Docking Simulation
Curcuma
Signal transduction
JNK Mitogen-Activated Protein Kinases
Macrophages
Cyclooxygenase 2
Molecular Dynamics Simulation
Interferons
Inhibitory Concentration 50
Lipopolysaccharides
Signal Transduction
Down-Regulation
Chemical activation
Proteins

Keywords

  • COX-2 mRNA expression
  • Dynamic simulation
  • MAPK phosphorylation
  • Molecular
  • Prostaglandin E
  • Unsymmetrical dicarbonyl curcumin derivatives

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives. / Mohd Aluwi, Mohd Fadhlizil Fasihi; Rullah, Kamal; Haque, Md Areeful; Mohd. Yamin, Bohari; Ahmad, Waqas; Amjad, Muhammad Wahab; Leong, Sze Wei; Fahmizar, Nurul Amira; Jalil, Juriyati; Abas, Faridah; Ismail, Nor Hadiani; Jantan, Ibrahim; Lam, Kok Wai.

In: Medicinal Chemistry Research, 18.08.2017, p. 1-13.

Research output: Contribution to journalArticle

Mohd Aluwi, MFF, Rullah, K, Haque, MA, Mohd. Yamin, B, Ahmad, W, Amjad, MW, Leong, SW, Fahmizar, NA, Jalil, J, Abas, F, Ismail, NH, Jantan, I & Lam, KW 2017, 'Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives', Medicinal Chemistry Research, pp. 1-13. https://doi.org/10.1007/s00044-017-2025-4
Mohd Aluwi, Mohd Fadhlizil Fasihi ; Rullah, Kamal ; Haque, Md Areeful ; Mohd. Yamin, Bohari ; Ahmad, Waqas ; Amjad, Muhammad Wahab ; Leong, Sze Wei ; Fahmizar, Nurul Amira ; Jalil, Juriyati ; Abas, Faridah ; Ismail, Nor Hadiani ; Jantan, Ibrahim ; Lam, Kok Wai. / Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives. In: Medicinal Chemistry Research. 2017 ; pp. 1-13.
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