Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents

Sze Wei Leong, Siti Munirah Mohd Faudzi, Faridah Abas, Mohd Fadhlizil Fasihi Mohd Aluwi, Kamal Rullah, Kok Wai Lam, Mohd Nazri Abdul Bahari, Syahida Ahmad, Chau Ling Tham, Khozirah Shaari, Nordin H. Lajis

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83, 84, 86, 88 and 97) exhibited greater or similar NO inhibitory activity in comparison with curcumin (14.7 ± 0.2 μM), notably compounds 88 and 97, which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 μM and 9.6 ± 0.5 μM, respectively. A structure-activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta- and para-positions of ring-B could be the marker for highly active diarylpentanoid derivatives.

Original languageEnglish
Pages (from-to)16058-16081
Number of pages24
JournalMolecules
Volume19
Issue number10
DOIs
Publication statusPublished - 1 Oct 2014

Fingerprint

Hydroxyl Radical
Anti-Inflammatory Agents
Electrons
analogs
Derivatives
Curcumin
Carrier concentration
rings
Structure-Activity Relationship
synthesis
Inhibitory Concentration 50
Lipopolysaccharides
Macrophages
retarding
Bioactivity
macrophages
Assays
markers
Molecules
molecules

Keywords

  • Anti-inflammatory
  • Curcumin
  • Diarylpentanoid
  • Pharmacophore
  • RAW 264.7
  • SAR

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Leong, S. W., Mohd Faudzi, S. M., Abas, F., Mohd Aluwi, M. F. F., Rullah, K., Lam, K. W., ... Lajis, N. H. (2014). Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents. Molecules, 19(10), 16058-16081. https://doi.org/10.3390/molecules191016058

Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents. / Leong, Sze Wei; Mohd Faudzi, Siti Munirah; Abas, Faridah; Mohd Aluwi, Mohd Fadhlizil Fasihi; Rullah, Kamal; Lam, Kok Wai; Abdul Bahari, Mohd Nazri; Ahmad, Syahida; Tham, Chau Ling; Shaari, Khozirah; Lajis, Nordin H.

In: Molecules, Vol. 19, No. 10, 01.10.2014, p. 16058-16081.

Research output: Contribution to journalArticle

Leong, SW, Mohd Faudzi, SM, Abas, F, Mohd Aluwi, MFF, Rullah, K, Lam, KW, Abdul Bahari, MN, Ahmad, S, Tham, CL, Shaari, K & Lajis, NH 2014, 'Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents', Molecules, vol. 19, no. 10, pp. 16058-16081. https://doi.org/10.3390/molecules191016058
Leong SW, Mohd Faudzi SM, Abas F, Mohd Aluwi MFF, Rullah K, Lam KW et al. Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents. Molecules. 2014 Oct 1;19(10):16058-16081. https://doi.org/10.3390/molecules191016058
Leong, Sze Wei ; Mohd Faudzi, Siti Munirah ; Abas, Faridah ; Mohd Aluwi, Mohd Fadhlizil Fasihi ; Rullah, Kamal ; Lam, Kok Wai ; Abdul Bahari, Mohd Nazri ; Ahmad, Syahida ; Tham, Chau Ling ; Shaari, Khozirah ; Lajis, Nordin H. / Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents. In: Molecules. 2014 ; Vol. 19, No. 10. pp. 16058-16081.
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