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

International Immunopharmacology
Zhixiang XuXiaohu Zhang

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 mechanistic studies indicated that compound 8 signifi...Continue Reading

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Citations

Mar 20, 2016·Molecular Neurobiology·Touqeer AhmedSeyed Mohammad Nabavi
May 25, 2015·Journal of Pharmacological Sciences·Ping GanLong Tai Zheng
Aug 1, 2016·Biochimica Et Biophysica Acta·N TalmaR H Henning
Jan 11, 2018·Cell Death & Disease·Xiaoyu WangXuechu Zhen

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