Tang Xue-Song, He Lin-Yu, Li Sheng-Nan, Zhang Wen-Cheng, Wu Ze-Yu, Hui Ai-Ling
Engineering Research Center of Bio-Process of Ministry of Education, School of Food and Biological Engineering, Hefei University of Technology, 420 Feicui Road, Hefei 230001, China.
Chem Biodivers. 2025 Mar;22(3):e202401931. doi: 10.1002/cbdv.202401931. Epub 2024 Nov 26.
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 C exhibited excellent acetylcholinesterase inhibitory activity (IC =1.16 0.41 μM) and anti-platelet aggregation activity (IC =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 C 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 C holds promise as a novel candidate drug for further investigation into the treatment of vascular dementia.
血管性痴呆（VaD）是一种由脑血管阻塞导致的神经退行性疾病，会引起认知障碍，目前缺乏有效的治疗方案。由于其发病机制复杂，多靶点药物设计（MTDLs）策略被认为是最有前景的治疗方法之一。在本研究中，我们设计并合成了一系列针对与血管健康和痴呆相关靶点的新型茚满酮衍生物。结果表明，化合物C在0.1 - 1000 μM和0.03 - 300 μM范围内分别表现出优异的乙酰胆碱酯酶抑制活性（IC = 1.16 ± 0.41 μM）和抗血小板聚集活性（IC = 4.92 ± 0.10 μM），这可能是由分子对接相互作用介导的。此外，化合物C在浓度≤50 μM时对细胞具有保护作用，以浓度依赖的方式显著降低一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的释放，显示出其强大的神经炎症抑制作用。抗炎疗法被认为是治疗VaD的有效策略。因此，化合物C有望作为一种新型候选药物，用于进一步研究血管性痴呆的治疗。
