Synthesis and Evaluation of Chalcone Derivatives as Inhibitors of Neutrophils' Chemotaxis, Phagocytosis and Production of Reactive Oxygen Species

• Published in: Chemical biology & drug design Vol. 83; no. 2; pp. 198 - 206
• Main Authors: Bukhari, Syed N. A., Tajuddin, Yasmin, Benedict, Vannessa J., Lam, Kok W., Jantan, Ibrahim, Jalil, Juriyati, Jasamai, Malina
• Format: Journal Article
• Language: English
• Published: HOBOKEN Blackwell Publishing Ltd 01.02.2014; Wiley
• Subjects: Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - pharmacology; Biochemistry & Molecular Biology; Cell Survival - drug effects; Chalcone - chemical synthesis; Chalcone - pharmacology; chalcones; Chemistry, Medicinal; chemotaxis; Chemotaxis, Leukocyte - drug effects; Ethanolamines - chemistry; Humans; Immunosuppressive Agents - chemical synthesis; Immunosuppressive Agents - pharmacology; inhibitors; Life Sciences & Biomedicine; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - metabolism; phagocytosis; Phagocytosis - drug effects; Pharmacology & Pharmacy; reactive oxygen species; Reactive Oxygen Species - metabolism; Science & Technology; Structure-Activity Relationship; chalcones; inhibitors; phagocytosis; CELLS; MOIETY; ANTIMICROBIAL EVALUATION; CHEMILUMINESCENCE; INFLAMMATION; reactive oxygen species; structure-activity relationship; CANCER; chemotaxis
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.12226

Inhibitory effects on neutrophils' chemotaxis, phagocytosis and production of reactive oxygen species (ROS) are among the important targets in developing anti‐inflammatory agents and immunosuppressants. Eight series of chalcone derivatives including five newly synthesized series were assessed for their inhibitory effects on chemotaxis, phagocytosis and ROS production in human polymorphonuclear neutrophils (PMNs). Inhibition of PMNs' chemotaxis and phagocytosis abilities were investigated using the Boyden chamber technique and the Phagotest kit, respectively, while ROS production was evaluated using luminol‐ and lucigenin‐based chemiluminescence assay. The new derivatives (4d and 8d), which contain 4‐methylaminoethanol functional group were active in all the assays performed. It was also observed that some of the compounds were active in inhibiting chemotaxis while others suppressed phagocytosis and ROS production. The information obtained gave new insight into chalcone derivatives with the potential to be developed as immunomodulators. Chalcone derivatives were synthesised and evaluated for their inhibitory effects on PMNs chemotaxis, phagocytosis and intracellular and extracellular ROS productions. It was observed that phenyl‐4‐methylaminoethanol and dimethoxy substituents contributed to these effects‥