title: Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents.
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.
authors.affiliation: Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. frederick_leong@hotmail.com.
authors.forename: Sze Wei
authors.initials: SW
authors.lastname: Leong
authors.affiliation: Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. munifaudzi@gmail.com.
authors.forename: Siti Munirah Mohd
authors.initials: SM
authors.lastname: Faudzi
authors.affiliation: Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. faridah_abas@upm.edu.my.
authors.forename: Faridah
authors.initials: F
authors.lastname: Abas
authors.affiliation: Drug and Herbal Research Centre Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abd. Aziz, 50300 Kuala Lumpur, Malaysia. fadhfasihi@yahoo.com.
authors.forename: Mohd Fadhlizil Fasihi Mohd
authors.initials: MF
authors.lastname: Aluwi
authors.affiliation: Drug and Herbal Research Centre Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abd. Aziz, 50300 Kuala Lumpur, Malaysia. kamalrullah@yahoo.co.id.
authors.forename: Kamal
authors.initials: K
authors.lastname: Rullah
authors.affiliation: Drug and Herbal Research Centre Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abd. Aziz, 50300 Kuala Lumpur, Malaysia. david_lam_98@yahoo.com.
authors.forename: Lam Kok
authors.initials: LK
authors.lastname: Wai
authors.affiliation: Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. nazribahari89@gmail.com.
authors.forename: Mohd Nazri Abdul
authors.initials: MN
authors.lastname: Bahari
authors.affiliation: Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. syahida@upm.edu.my.
authors.forename: Syahida
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. chauling@upm.edu.my.
authors.forename: Chau Ling
authors.initials: CL
authors.lastname: Tham
authors.affiliation: Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. khozirah@upm.edu.my.
authors.forename: Khozirah
authors.initials: K
authors.lastname: Shaari
authors.affiliation: 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. nordinlajis@gmail.com.
authors.forename: Nordin H
authors.initials: NH
authors.lastname: Lajis
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology; D004355:Drug Stability; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D007371:Interferon-gamma; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D007371:Interferon-gamma; D003474:Curcumin