Design, Synthesis, and Mechanism of Dihydroartemisinin⁻Coumarin Hybrids as Potential Anti-Neuroinflammatory Agents

双氢青蒿素⁻香豆素杂化物作为潜在抗神经炎药的设计、合成及作用机理

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作者:Haonan Yu, Zhuang Hou, Xiaoguang Yang, Yanhua Mou, Chun Guo

Abstract

Cancer patients frequently suffer from cancer-related fatigue (CRF), which is a complex syndrome associated with weakness and depressed mood. Neuroinflammation is one of the major inducers of CRF. The aim of this study is to find a potential agent not only on the treatment of cancer, but also for reducing CRF level of cancer patients. In this study, total-thirty new Dihydroartemisinin-Coumarin hybrids (DCH) were designed and synthesized. The in vitro cytotoxicity against cancer cell lines (HT-29, MDA-MB-231, HCT-116, and A549) was evaluated. Simultaneously, we also tested the anti-neuroinflammatory activity of DCH. DCH could inhibit the activated microglia N9 release of NO, TNF-α, and IL-6. The docking analysis was shown that MD-2, the coreceptor of TLR4, might be one of the targets of DCH.

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