Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: Synthesis, biological activity, crystal structure, and in silico evaluation

Kamal Rullah, Mohd Fadhlizil Fasihi Mohd Aluwi, Bohari Mohd. Yamin, Mohd Nazri Abdul Bahari, Leong Sze Wei, Syahida Ahmad, Faridah Abas, Nor Hadiani Ismail, Ibrahim Jantan, Kok Wai Lam

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The discovery of potent inhibitors of prostaglandin E2 (PGE 2) synthesis in recent years has been proven to be an important game changer in pharmaceutical industry. It is known that excessive production of PGE2 triggers a vast array of biological signals and physiological events that contributes to inflammatory diseases such as rheumatoid arthritis, atherosclerosis, cancer, and pain. In this Letter, we report the synthesis of a series of minor prenylated chalcones and flavonoids which was found to be significantly active in suppressing the PGE2 production secreted by lipopolysaccharide-induced mouse macrophage cells (RAW 264.7). Among the compounds tested, 14b showed a dose-response inhibition of PGE2 production with an IC50 value of 2.1 μM. The suppression upon PGE2 secretion was not due to cell death since 14b did not reduce the cell viability in close proximity to the PGE2 inhibition concentration. The obtained atomic coordinates for the single-crystal XRD of 14b was then applied in the docking simulation to determine the potential important binding interactions with murine COX-2 and mPGES-1 putative binding sites.

Original languageEnglish
Pages (from-to)3826-3834
Number of pages9
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number16
DOIs
Publication statusPublished - 15 Aug 2014

Fingerprint

Chalcones
Bioactivity
Dinoprostone
Flavonoids
Computer Simulation
Crystal structure
Macrophages
Drug Industry
Cell death
Inhibitory Concentration 50
Lipopolysaccharides
Inhibition (Psychology)
Rheumatoid Arthritis
Cell Survival
Atherosclerosis
Cell Death
Binding Sites
Cells
Single crystals
Pharmaceutical Preparations

Keywords

  • ADMET prediction
  • COX-2 inhibitor
  • Minor flavonoids
  • Prenylated chalcone
  • Single-crystal XRD

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

Cite this

Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids : Synthesis, biological activity, crystal structure, and in silico evaluation. / Rullah, Kamal; Mohd Aluwi, Mohd Fadhlizil Fasihi; Mohd. Yamin, Bohari; Abdul Bahari, Mohd Nazri; Wei, Leong Sze; Ahmad, Syahida; Abas, Faridah; Ismail, Nor Hadiani; Jantan, Ibrahim; Lam, Kok Wai.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 16, 15.08.2014, p. 3826-3834.

Research output: Contribution to journalArticle

Rullah, Kamal ; Mohd Aluwi, Mohd Fadhlizil Fasihi ; Mohd. Yamin, Bohari ; Abdul Bahari, Mohd Nazri ; Wei, Leong Sze ; Ahmad, Syahida ; Abas, Faridah ; Ismail, Nor Hadiani ; Jantan, Ibrahim ; Lam, Kok Wai. / Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids : Synthesis, biological activity, crystal structure, and in silico evaluation. In: Bioorganic and Medicinal Chemistry Letters. 2014 ; Vol. 24, No. 16. pp. 3826-3834.
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