Design, synthesis and evaluation of a series of non-steroidal anti-inflammatory drug conjugates as novel neuroinflammatory inhibitors.

Design, synthesis and evaluation of a series of non-steroidal anti-inflammatory drug conjugates as novel neuroinflammatory inhibitors. Int Immunopharmacol. 2015 Mar 10;25(2):528-537 Authors: Xu Z, Wu J, Zheng J, Ma H, Zhang H, Zhen X, Zheng LT, Zhang X Abstract Neuroinflammation is involved in the process of several central nervous system (CNS) diseases such as Parkinson's disease, Alzheimer's disease, ischemia and multiple sclerosis. As the macrophages in the central nervous system, microglial cell function in the innate immunity of the brain and are largely responsible for the inflammation-mediated neurotoxicity. Prevention of microglia activation might alleviate neuronal damage and degeneration under the inflammatory conditions, and therefore, represents a possible therapeutic approach to the aforementioned CNS diseases. Here we report the synthesis of a number of non-steroidal anti-inflammatory drug (NSAID) conjugates, and the evaluation of their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and primary mouse microglial cells. Among the tested analogues, compounds 8 and 11 demonstrated potent inhibition of nitric oxide production with no or weak cell toxicity. Compound 8 also significantly suppressed the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, cyclooxygenase (COX)-2 as well as inducible nitric oxide synthase (iNOS) in LPS-stimulated BV-2 microglial cells. Further ...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research