Tang_2024_Chem.Biodivers__e202401931

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 microM) and anti-platelet aggregation activity (IC50 = 4.92 +/- 0.10 microM) within ranges of 0.1-1000 microM and 0.03-300 microM, respectively, possibly mediated by molecular docking interactions. Furthermore, compound C5 demonstrated protective effects on cells at concentrations >=50 microM, significantly reducing the release of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1beta) 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.