The Anti-Inflammatory Activities of Benzylideneacetophenone Derivatives in LPS Stimulated BV2 Microglia Cells and Mice.

Abstract

A previously reported study highlighted the neuroprotective potential of the novel benzylideneacetophenone derivative, JC3, in mice. In pursuit of compounds with even more robust neuroprotective and anti-inflammatory properties compared to JC3, we synthesized substituted 1,3-diphenyl-2-propen-1-ones based on chalcones. Molecular modeling studies aimed at discerning the chemical structural features conducive to heightened biological activity revealed that JCII-8,10,11 exhibited the widest HOMOLUMO gap within this category, indicating facile electron and radical transfer between HOMO and LUMO in model assessments. From the pool of synthesized compounds, JCII-8,10,11 were selected for the present investigation. The biological assays involving JCII-8,10,11 demonstrated their concentration-dependent suppression of iNOS and COX-2 protein levels, alongside various cytokine mRNA expressions in LPS-induced murine microglial BV2 cells. Furthermore, western blot analyses were conducted to investigate the MAPK pathways and NF-κB/p65 nuclear translocation. These evaluations conclusively confirmed the inflammatory inhibition effects in both in vitro and in vivo inflammation models. These findings establish JCII-8,10,11 as potent anti-inflammatory agents, hindering inflammatory mediators and impeding NF-κB/p65 nuclear translocation via JNK and ERK MAPK phosphorylation in BV2 cells. The study positions them as potential therapeutics for inflammation-related conditions. Additionally, JCII-11 exhibited greater activity compared to other tested JCII compounds.