Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh.
Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh.
Oxid Med Cell Longev. 2022 Aug 18;2022:7252882. doi: 10.1155/2022/7252882. eCollection 2022.
Tacrine is a drug used in the treatment of Alzheimer's disease as a cognitive enhancer and inhibitor of the enzyme acetylcholinesterase (AChE). However, its clinical application has been restricted due to its poor therapeutic efficacy and high prevalence of detrimental effects. An attempt was made to understand the molecular mechanisms that underlie tacrine and its analogues influence over neurotherapeutic activity by focusing on modulation of neurogenesis, neuroinflammation, endoplasmic reticulum stress, apoptosis, and regulatory role in gene and protein expression, energy metabolism, Ca homeostasis modulation, and osmotic regulation. Regardless of this, analogues of tacrine are considered as a model inhibitor of cholinesterase in the therapy of Alzheimer's disease. The variety both in structural make-up and biological functions of these substances is the main appeal for researchers' interest in them. A new paradigm for treating neurological diseases is presented in this review, which includes treatment strategies for Alzheimer's disease, as well as other neurological disorders like Parkinson's disease and the synthesis and biological properties of newly identified versatile tacrine analogues and hybrids. We have also shown that these analogues may have therapeutic promise in the treatment of neurological diseases in a variety of experimental systems.
他克林是一种用于治疗阿尔茨海默病的药物，作为认知增强剂和乙酰胆碱酯酶 (AChE) 的抑制剂。然而，由于其治疗效果不佳和不良反应发生率高，其临床应用受到限制。本研究试图通过关注神经发生、神经炎症、内质网应激、细胞凋亡以及对基因和蛋白质表达、能量代谢、钙稳态调节和渗透调节的调节作用，来理解他克林及其类似物对神经治疗活性的影响的分子机制。尽管如此，他克林的类似物仍被认为是治疗阿尔茨海默病的胆碱酯酶的模型抑制剂。这些物质在结构组成和生物学功能上的多样性是引起研究人员兴趣的主要原因。本综述提出了一种治疗神经疾病的新范式，包括阿尔茨海默病的治疗策略，以及其他神经疾病，如帕金森病，以及新鉴定的多功能他克林类似物和杂种的合成和生物学特性。我们还表明，这些类似物在多种实验系统中可能具有治疗神经疾病的潜力。
