2. Academic Validation
  3. Anti-neuroinflammatory effects of novel 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives in lipopolysaccharide-stimulated BV2 microglial cells

Anti-neuroinflammatory effects of novel 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives in lipopolysaccharide-stimulated BV2 microglial cells

  • Eur J Med Chem. 2022 May 5;235:114322. doi: 10.1016/j.ejmech.2022.114322.
Xiao-Fan Zhang 1,  Ming-Zhu Luan 1,  Wei-Bin Yan 2,  Feng-Lan Zhao 1,  Yun Hou 2,  Gui-Ge Hou 3,  Qing-Guo Meng 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China.
  • 2 School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, PR China.
  • 3 School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, PR China. Electronic address: guigehou@163.com.
  • 4 School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China. Electronic address: qinggmeng@163.com.
PMID: 35367709 DOI: 10.1016/j.ejmech.2022.114322
Abstract

Neuroinflammation is an intricate process that is associated with both normal and pathological conditions. Microglia-mediated neuroinflammation is known to lead to various neurodegenerative and neurological disorders. A series of 3,4-dihydronaphthalen-1(2H)-one derivatives (1-15) and novel 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives (16-30) were synthesized and characterized by various analytical methods, such as NMR and HRMS. All compounds were evaluated for toxicity, screened for their anti-neuroinflammatory properties, and investigated for the potential molecular mechanism of lipopolysaccharide (LPS) induction in BV2 microglia. Structure activity relationship analysis showed that compound 17 substituted by the 7-fluorine atom on the A-ring and the 3-methoxy on the D-ring had more potential anti-neuroinflammatory activity by inhibiting the secretion of cytokines TNF-α and IL-6. The results of western blotting assay showed that 17 significantly blocked the activation and phosphorylation of IκBα, significantly reduce the expression of NLRP3 inflammatory vesicle-associated proteins, and thus inhibit the activation of NF-κB pathway. Thus, compound 17 was demonstrated to be an excellent potential therapeutic agent for the treatment of neuroinflammation-related diseases.

Keywords

3,4-dihydronaphthalen-1(2H)-one; Anti-neuroinflammation; BV2 microglial cells; NF-κB inhibitor.

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