Journal Article

Studies of synthetic chalcone derivatives as potential inhibitors of secretory phospholipase A2, cyclooxygenases, lipoxygenase and pro-inflammatory cytokines

Jantan, Ibrahim, Sylte, Ingebrigt, Adekoya, Layi, Bukhari, Syed

2014

Overview

Arachidonic acid metabolism leads to the generation of key lipid mediators which play a fundamental role during inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as a synergistic anti-inflammatory effect with enhanced spectrum of activity. A series of 1,3-diphenyl-2-propen-1-one derivatives were investigated for anti-inflammatory related activities involving inhibition of secretory phospholipase A2, cyclooxygenases, soybean lipoxygenase, and lipopolysaccharides-induced secretion of interleukin-6 and tumor necrosis factor-alpha in mouse RAW264.7 macrophages. The results from the above mentioned assays exhibited that the synthesized compounds were effective inhibitors of pro-inflammatory enzymes and cytokines. The results also revealed that the chalcone derivatives with 4-methlyamino ethanol substitution seem to be significant for inhibition of enzymes and cytokines. Molecular docking experiments were carried out to elucidate the molecular aspects of the observed inhibitory activities of the investigated compounds. Present findings increase the possibility that these chalcone derivatives might serve as a beneficial starting point for the design and development of improved anti-inflammatory agents.

• Publisher: Taylor & Francis Ltd,Dove Press,Dove Medical Press
• Subject: Acids / Animals / anti-inflammatory / Anti-inflammatory agents / Anti-Inflammatory Agents - chemical synthesis / Anti-Inflammatory Agents - chemistry / Anti-Inflammatory Agents - pharmacology / Arachidonic acid / Cell adhesion & migration / Chalcone - analogs & derivatives / Chalcone - chemical synthesis / Chalcone - chemistry / Chalcone - pharmacology / Cyclooxygenase Inhibitors - chemical synthesis / Cyclooxygenase Inhibitors - chemistry / Cyclooxygenase Inhibitors - pharmacology / Cytokines / Cytokines - antagonists & inhibitors / Cytokines - metabolism / Derivatives / Enzymes / Ethanol / Flavonoids / Gene expression / Humans / Inflammation / Inflammatory diseases / Inhibition / Inhibitors / Interleukin 6 / Lipids / Lipopolysaccharides / Lipoxygenase / Lipoxygenase - metabolism / Lipoxygenase Inhibitors - chemical synthesis / Lipoxygenase Inhibitors - chemistry / Lipoxygenase Inhibitors - pharmacology / Macrophages / Macrophages - drug effects / Macrophages - metabolism / Metabolism / Mice / Molecular docking / Neutrophils / Original Research / Pain / Pharmacy / Phospholipase / Phospholipase A2 / Phospholipase A2 Inhibitors - chemical synthesis / Phospholipase A2 Inhibitors - chemistry / Phospholipase A2 Inhibitors - pharmacology / Phospholipases A2, Secretory - antagonists & inhibitors / Phospholipases A2, Secretory - metabolism / Prostaglandin-Endoperoxide Synthases - metabolism / Rheumatoid arthritis / Soybeans / tumor necrosis factor-alpha / Tumor necrosis factor-TNF / Tumor necrosis factor-α