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

Molecules. 2019 Apr 28;24(9):1672. doi: 10.3390/molecules24091672.

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.

Keywords: anti-neuroinflammation; anticancer; coumarin; dihydroartemisinin.

MeSH terms

  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology*
  • Artemisinins / chemical synthesis
  • Artemisinins / chemistry*
  • Artemisinins / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coumarins / chemical synthesis
  • Coumarins / chemistry*
  • Coumarins / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents
  • Artemisinins
  • Coumarins
  • artenimol
  • coumarin