Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal Dir (Upper), Dir 18000, Pakistan.
Department of Pharmacy, University of Malakand Dir (Lower), Chakdara 18800, Pakistan.
Molecules. 2022 Apr 11;27(8):2468. doi: 10.3390/molecules27082468.
Alzheimer’s disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a−1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inhibition of cholinesterase(s). It has been indicated from the current research work that the synthesized curcumin analogs enhanced memory functions in mice models and could be used as valuable therapeutic molecules against neurodegenerative disorders. To determine their exact mechanism of action, further studies are suggested.
阿尔茨海默病是一种与认知能力下降和记忆力丧失相关的新兴健康障碍。在这项研究中，合成了六种姜黄素类似物（1a-1f），并对其体外乙酰胆碱酯酶抑制潜力进行了筛选。基于有希望的结果，使用高架十字迷宫（EPM）、Y 迷宫和新物体识别（NOR）行为模型对它们进行了进一步的体内分析研究。确定了合成化合物与乙酰胆碱酯酶活性部位的结合模式，以及胆碱能系统在大脑海马体中的参与。合成的姜黄素类似物 1d（p<0.001，n=6）和 1c（p<0.01，n=6）通过减少 EPM 中的保留时间、显著增加 Y 迷宫中的 SAP%，同时显著（p<0.001）提高 NOR 中 %辨别指数（DI）和探索新物体的时间，从而显示出有希望的结果。使用 MOE 软件进行的分子对接研究用于验证对乙酰胆碱酯酶的抑制作用。目前的研究工作表明，合成的姜黄素类似物增强了小鼠模型的记忆功能，可作为治疗神经退行性疾病的有价值的治疗分子。为了确定它们的确切作用机制，建议进行进一步的研究。
