Sağlık Begüm Nurpelin, Levent Serkan, Osmaniye Derya, Evren Asaf Evrim, Karaduman Abdullah Burak, Özkay Yusuf, Kaplancıklı Zafer Asım
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
Central Research Laboratory (MERLAB), Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
ACS Omega. 2022 Dec 7;7(50):47378-47404. doi: 10.1021/acsomega.2c06906. eCollection 2022 Dec 20.
Alzheimer's disease (AD) is a neurological, progressive illness that typically affects the elderly and is clinically distinguished by memory and cognitive decline. Due to a number of factors, including the absence of a radical treatment, an increase in the patient population over time, the high cost of care and treatment, and a significant decline in patients' quality of life, the importance of this disease has increased. These factors have all prompted increased interest among researchers in this field. The chemical structure of the donepezil molecule, the most popular and effective treatment response for AD, served as the basis for the design and synthesis of 42 novel indan-1-one derivatives in this study. Using IR, H, and C NMR as well as mass spectroscopic techniques, the compounds' structures were identified. Research on the compounds' antioxidant activities, cholinesterase (ChE) enzyme inhibition, monoamine oxidase (MAO) A and B inhibitory activities, β-amyloid plaque inhibition, and cytotoxicity impact was carried out. Inhibition of β-amyloid plaque aggregation; effective inhibition of AChE, BChE, and MAO-B enzymes; and significant antioxidant activity were all demonstrated by compounds - and -. Because of their various actions, it was hypothesized that the related compounds may be useful in treating AD symptoms as well as providing palliative care.
阿尔茨海默病(AD)是一种神经退行性疾病,通常影响老年人,临床特征为记忆和认知能力下降。由于多种因素,包括缺乏根治性治疗方法、患者数量随时间增加、护理和治疗成本高昂以及患者生活质量显著下降,这种疾病的重要性日益凸显。这些因素促使该领域的研究人员对其兴趣大增。本研究中,多奈哌齐分子(AD最常用且有效的治疗药物)的化学结构成为设计和合成42种新型茚满-1-酮衍生物的基础。利用红外光谱(IR)、氢核磁共振(H NMR)、碳核磁共振(C NMR)以及质谱技术确定了这些化合物的结构。对这些化合物的抗氧化活性、胆碱酯酶(ChE)抑制作用、单胺氧化酶(MAO)A和B抑制活性、β-淀粉样蛋白斑块抑制作用以及细胞毒性影响进行了研究。化合物 - 和 - 均表现出抑制β-淀粉样蛋白斑块聚集、有效抑制乙酰胆碱酯酶(AChE)、丁酰胆碱酯酶(BChE)和单胺氧化酶B(MAO-B)以及显著的抗氧化活性。鉴于其多种作用,推测相关化合物可能有助于治疗AD症状并提供姑息治疗。