Potential anti-neuroinflammatory NF-кB inhibitors based on 3,4-dihydronaphthalen-1(2H)-one derivatives

Abstract

Nuclear factor kappa B (NF-rB) inhibition represents a new therapeutic strategy for the treatment of neuroinflammatory diseases. In this study, a series of 3,4-dihydronaphthalen-1(2H)-one (DHN; 6a-n, 7a-c) derivatives were synthesised and characterised by NMR and HRMS. We assessed the toxicity and anti-neuroinflammatory properties of these compounds and found that 6m showed the greatest anti-neuroinflammatory properties, with relatively low toxicity. Specifically, 6m significantly reduced reactive oxygen species production, down-regulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 and prevented lipopolysaccharide-stimulated BV2 microglia cells polarisation towards an M1 phenotype. Furthermore, 6m significantly decreased IjBa and NF-rB p65 phosphorylation, thus inhibiting the NF-rB signalling pathway. This suggests that 6m may be explored as a functional anti-neuroinflammatory agent for the treatment of inflammatory diseases in the central nervous system, such as multiple sclerosis, traumatic brain injury, stroke and spinal cord injury.

Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study

“…It exhibits a broad spectrum of anticancer and antimicrobial activity [ 14 , 15 , 16 , 17 , 18 , 19 ]. On the other hand, there are reports in the scientific literature about dihydronaphthalene showing biological activity [ 30 , 31 , 32 ].…”

Correlation of the prognostic value of FNDC4 in glioblastoma with macrophage polarization

“…These macrophages secrete important transforming factors, cytokines, and chemokines to activate signaling molecules that induce the proliferation of tumor cells and increase the degree of tumor malignancy [ 41 – 43 ]. In the TIM of glioblastoma, M1-type microglia exert antitumor immune functions by producing proinflammatory cytokines [ 44 , 45 ] and transcription signals as well as STAT1 [ 46 – 48 ]. However, in the present study, we found that FNDC4 promoted only the proliferation of glioblastoma cells, the potential mechanism associated with which may be related to the observed inhibition of M1 macrophage polarization by exocrine FNDC4.…”

Crystal structure of (E)-2-((2-methoxy-3-pyridyl)methylene)-7-fluoro-3,4-dihydronaphthalen-1(2H)-one, C17H14FNO2

“…In addition, activated microglia can produce reactive oxygen species (ROS), which may indirectly induce neuroinflammation by activating NF-κB [10,11]. Therefore, NF-κB inhibitor with anti-neuroinflammatory activity may represent a therapeutic option for the treatment of inflammatory neurodegenerative diseases [12][13][14].…”