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 language | English |
|---|---|
| Pages (from-to) | 16058-16081 |
| Number of pages | 24 |
| Journal | Molecules |
| Volume | 19 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 1 Oct 2014 |
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Keywords
- Anti-inflammatory
- Curcumin
- Diarylpentanoid
- Pharmacophore
- RAW 264.7
- SAR
ASJC Scopus subject areas
- Organic Chemistry
Cite this
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 journal › Article
}
TY - JOUR
T1 - Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents
AU - Leong, Sze Wei
AU - Mohd Faudzi, Siti Munirah
AU - Abas, Faridah
AU - Mohd Aluwi, Mohd Fadhlizil Fasihi
AU - Rullah, Kamal
AU - Lam, Kok Wai
AU - Abdul Bahari, Mohd Nazri
AU - Ahmad, Syahida
AU - Tham, Chau Ling
AU - Shaari, Khozirah
AU - Lajis, Nordin H.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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.
AB - 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.
KW - Anti-inflammatory
KW - Curcumin
KW - Diarylpentanoid
KW - Pharmacophore
KW - RAW 264.7
KW - SAR
UR - http://www.scopus.com/inward/record.url?scp=84911922324&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84911922324&partnerID=8YFLogxK
U2 - 10.3390/molecules191016058
DO - 10.3390/molecules191016058
M3 - Article
C2 - 25302700
AN - SCOPUS:84911922324
VL - 19
SP - 16058
EP - 16081
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 10
ER -