Design, Synthesis, and Anti-Inflammatory Activity Evaluation of Novel Indanone Derivatives for the Treatment of Vascular Dementia

Vascular dementia (VaD) is a neurodegenerative disease resulting from cerebral vascular obstruction, leading to cognitive impairment, and currently lacks effective treatment options. Due to its complex pathogenesis, multi-target drug design (MTDLs) strategies are considered among the most promising therapeutic approaches. In this study, we designed and synthesized a series of novel indanone derivatives targeting targets related to vascular health and dementia. The results indicated that compound C₅ exhibited excellent acetylcholinesterase inhibitory activity (IC₅₀ =1.16 0.41 μM) and anti-platelet aggregation activity (IC₅₀ =4.92±0.10 μM) within ranges of 0.1-1000 μM and 0.03-300 μM, respectively, possibly mediated by molecular docking interactions. Furthermore, compound C₅ demonstrated protective effects on cells at concentrations ≤50 μM, significantly reducing the release of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) in a concentration-dependent manner, showcasing its potent neuroinflammatory inhibitory effects. Anti-inflammatory therapies are regarded as effective strategies for treating VaD. Therefore, compound C₅ holds promise as a novel candidate drug for further investigation into the treatment of vascular dementia.