Recent advances in the therapeutic insights of thiazole scaffolds as acetylcholinesterase inhibitors

IF 5.9 2区 医学 Q1 CHEMISTRY, MEDICINAL European Journal of Medicinal Chemistry Pub Date : 2025-04-05 Epub Date: 2025-01-30 DOI:10.1016/j.ejmech.2025.117331
Dina H. Dawood , Manal M. Anwar
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Abstract

Suppression of the acetylcholinesterase (AChE) enzyme is a prevalent strategy for curing diverse mental disorders, including Alzheimer's disease (AD) and the chronic autoimmune disease Myasthenia gravis. Acetylcholinesterase inhibitors promote cholinergic transmission via blocking AChE, which is implicated in the degradation and deficiency of acetylcholine. Various studies proved that the lack of cholinergic neurons in the central nervous system is the substantial reason for the behavioral abnormalities and cognitive retogradation that distinguish mental diseases such as dementia and AD. Moreover, thiazole scaffolds have emerged as prominent pharmacophores in drug discovery owing to their numerous outstanding therapeutic efficacy, comprising anti-acetylcholinesterase efficacy. This review presents various thiazole-based AChE inhibitors in the recent decade. In addition, the various interactions of thiazole derivatives within the active pocket of AChE have been highlighted. Also, structure-activity relationship (SAR) has been discussed.

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噻唑支架作为乙酰胆碱酯酶抑制剂的研究进展
抑制乙酰胆碱酯酶(AChE)是治疗多种精神障碍的普遍策略,包括阿尔茨海默病(AD)和慢性自身免疫性疾病重症肌无力。乙酰胆碱酯酶抑制剂通过阻断乙酰胆碱酯酶促进胆碱能传递,这与乙酰胆碱的降解和缺乏有关。各种研究证明,中枢神经系统胆碱能神经元的缺乏是区分痴呆和AD等精神疾病的行为异常和认知退化的实质原因。此外,噻唑支架已成为药物发现中突出的药效载体,因为它们具有许多突出的治疗功效,包括抗乙酰胆碱酯酶的功效。本文综述了近十年来噻唑类乙酰胆碱酯酶抑制剂的研究进展。此外,还强调了乙酰胆碱酯活性口袋内噻唑衍生物的各种相互作用。
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来源期刊
CiteScore
11.70
自引率
9.00%
发文量
863
审稿时长
29 days
期刊介绍: The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.
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