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

Leong, Sze Wei and Mohd Faudzi, Siti Munirah and Abas, Faridah and Mohd Aluwi, Mohd Fadhlizil Fasihi and Rullah, Kamal and Lam, Kok Wai and Abdul Bahari, Mohd Nazri and Ahmad, Syahida and Chau, Ling Tham and Shaari, Khozirah and Lajis, Nordin H. (2014) Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents. Molecules, 19 (10). pp. 16058-16081. E-ISSN 1420-3049

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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

Item Type:	Article (Journal)
Additional Information:	9020/73537
Uncontrolled Keywords:	Anti-inflammatory; diarylpentanoid; RAW 264.7; curcumin; SAR; pharmacophore
Subjects:	R Medicine > RS Pharmacy and materia medica > RS403 Materia Medica-Pharmaceutical Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry Kulliyyah of Pharmacy
Depositing User:	Dr Kamal Rullah
Date Deposited:	07 Aug 2019 11:35
Last Modified:	07 Aug 2019 11:35
URI:	http://irep.iium.edu.my/id/eprint/73537

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