Synthesis and Sar Study of Diarylpentanoid Analogues as New Anti-Inflammatory Agents

Molecules

Sze Wei Leong¹  Siti Munirah Mohd Faudzi¹  Faridah Abas¹  Mohd Fadhlizil Fasihi Mohd Aluwi³  Kamal Rullah³  Lam Kok Wai³  Mohd Nazri Abdul Bahari⁴  Syahida Ahmad⁴  Chau Ling Tham⁵  Khozirah Shaari¹  Nordin H. Lajis² 

[1] Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; E-Mails:;Al-Moalim BinLaden Chair for Scientific Miracles of Prophetic Medicine, Scientific Chairs Unit, Taibah University, P.O. Box 30001, Madinah al Munawarah 41311, Saudi Arabia;Drug and Herbal Research Centre Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abd. Aziz, 50300 Kuala Lumpur, Malaysia; E-Mails:;Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; E-Mails:;Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; E-Mail:

关键词: anti-inflammatory;    diarylpentanoid;    RAW 264.7;    curcumin;    SAR;    pharmacophore;   

DOI  :  10.3390/molecules191016058

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.