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新型以 -Boc-保护的脯氨酸为配体的金(I)和银(I)-氮杂环卡宾配合物作为神经退行性疾病的潜在候选物

Novel Au(I)- and Ag(I)-NHC Complexes with -Boc-Protected Proline as Potential Candidates for Neurodegenerative Disorders.

作者信息

Ceramella Jessica, D'Amato Assunta, Procopio Francesca, Mariconda Annaluisa, Chavarria Daniel, Iacopetta Domenico, Ortuso Francesco, Longo Pasquale, Borges Fernanda, Sinicropi Maria Stefania

机构信息

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, Italy.

Department of Chemistry and Biology "A. Zambelli", University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy.

出版信息

Int J Mol Sci. 2025 Jun 25;26(13):6116. doi: 10.3390/ijms26136116.

Abstract

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by progressive neuronal dysfunction and loss and represent a significant global health challenge. Oxidative stress, neuroinflammation, and neurotransmitter dysregulation, particularly affecting acetylcholine (ACh) and monoamines, are key hallmarks of these conditions. The current therapeutic strategies targeting cholinergic and monoaminergic systems have some limitations, highlighting the need for novel approaches. Metallodrugs, especially ruthenium and platinum complexes, are gaining attention for their therapeutic use. Among metal complexes, gold(I) and silver(I) -heterocyclic carbene (NHC) complexes exhibit several biological activities, but their application in NDDs, particularly as monoamine oxidase (MAO) inhibitors, remains largely unexplored. To advance the understanding of this field, we designed, synthesized, and evaluated the biological activity of a new series of Au(I) and Ag(I) complexes stabilized by NHC ligands and bearing a carboxylate salt of tert-butyloxycarbonyl (Boc)--protected proline as an anionic ligand. Through in silico and in vitro studies, we assessed their potential as acetylcholinesterase (AChE) and MAO inhibitors, as well as their antioxidant and anti-inflammatory properties, aiming to contribute to the development of potential novel therapeutic agents for NDD management.

摘要

神经退行性疾病(NDDs),包括阿尔茨海默病(AD)和帕金森病(PD),其特征是神经元功能逐渐失调和丧失,是全球重大的健康挑战。氧化应激、神经炎症和神经递质失调,特别是影响乙酰胆碱(ACh)和单胺,是这些病症的关键特征。目前针对胆碱能和单胺能系统的治疗策略存在一些局限性,这凸显了对新方法的需求。金属药物,尤其是钌和铂配合物,因其治疗用途而受到关注。在金属配合物中,金(I)和银(I)-杂环卡宾(NHC)配合物表现出多种生物活性,但它们在NDDs中的应用,特别是作为单胺氧化酶(MAO)抑制剂,在很大程度上仍未得到探索。为了推进对该领域的理解,我们设计、合成并评估了一系列由NHC配体稳定且带有叔丁氧羰基(Boc)保护的脯氨酸羧酸盐作为阴离子配体的新型金(I)和银(I)配合物的生物活性。通过计算机模拟和体外研究,我们评估了它们作为乙酰胆碱酯酶(AChE)和MAO抑制剂的潜力,以及它们的抗氧化和抗炎特性,旨在为开发用于管理NDDs的潜在新型治疗药物做出贡献。

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