Design, synthesis and evaluation of a novel metal chelator as multifunctional agents for the treatment of Alzheimer’s disease

Wang, Yingying; Yang, Yue; Hong, Kwon Ho; Ning, Yao; Yu, Ping; Ren, Jinghui; Ji, Min; Cai, Jin

doi:10.1016/j.bioorg.2019.03.064

Cited by 17 publications

(8 citation statements)

References 41 publications

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“…DPPH assay was used to evaluate the free radical scavenging ability of the representative compound 10a , while Trolox was used as a control [ 33 ]. As shown in Table 2 , compound 10a displayed moderate radical scavenging activity (31.89% ± 3.23% at 50 μM).…”

Section: Resultsmentioning

confidence: 99%

Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one

Jia

et al. 2022

Molecules

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Alzheimer’s disease (AD) is a neurodegenerative disease that causes memory and cognitive decline as well as behavioral problems. It is a progressive and well recognized complex disease; therefore, it is very urgent to develop novel and effective anti-AD drugs. In this study, a series of novel isochroman-4-one derivatives from natural (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] were designed and synthesized, and their anti-AD potential was evaluated. Among them, compound 10a [(Z)-3-acetyl-1-benzyl-4-((6,7-dimethoxy-4-oxoisochroman-3-ylidene)methyl)pyridin-1-ium bromide] possessed potent anti-acetylcholinesterase (AChE) activity as well as modest antioxidant activity. Further molecular modeling and kinetic investigations revealed that compound 10a was a dual-binding inhibitor that binds to both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the enzyme AChE. In addition, compound 10a exhibited low cytotoxicity and moderate anti-Aβ aggregation efficacy. Moreover, the in silico screening suggested that these compounds could pass across the blood–brain barrier with high penetration. These findings show that compound 10a was a promising lead from a natural product with potent AChE inhibitory activity and deserves to be further developed for the prevention and treatment of AD.

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Section: Resultsmentioning

confidence: 99%

Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one

Jia

et al. 2022

Molecules

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“…In addition, an NP-iron chelator was synthesized and coated with polysorbate 80 so that the nanoformulation could easily cross the BBB [206]. Similarly, in other studies, chelators, such as xanthone derivatives, deferasirox, deferoxamine, iodochlorhydroxyquin, and tacrine, reduced AchE inhibited ROS production and showed potent anti-Alzheimer's effects [207,208].…”

Section: Np-chelation-based Ad Therapymentioning

confidence: 98%

Mechanisms Involved in Microglial-Interceded Alzheimer’s Disease and Nanocarrier-Based Treatment Approaches

Shadab

Alhakamy

Alfaleh

et al. 2021

JPM

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Alzheimer’s disease (AD) is a common neurodegenerative disorder accountable for dementia and cognitive dysfunction. The etiology of AD is complex and multifactorial in origin. The formation and deposition of amyloid-beta (Aβ), hyperphosphorylated tau protein, neuroinflammation, persistent oxidative stress, and alteration in signaling pathways have been extensively explored among the various etiological hallmarks. However, more recently, the immunogenic regulation of AD has been identified, and macroglial activation is considered a limiting factor in its etiological cascade. Macroglial activation causes neuroinflammation via modulation of the NLRP3/NF-kB/p38 MAPKs pathway and is also involved in tau pathology via modulation of the GSK-3β/p38 MAPK pathways. Additionally, microglial activation contributes to the discrete release of neurotransmitters and an altered neuronal synaptic plasticity. Therefore, activated microglial cells appear to be an emerging target for managing and treating AD. This review article discussed the pathology of microglial activation in AD and the role of various nanocarrier-based anti-Alzeihmenr’s therapeutic approaches that can either reverse or inhibit this activation. Thus, as a targeted drug delivery system, nanocarrier approaches could emerge as a novel means to overcome existing AD therapy limitations.

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“…In another study, deferasirox and tacrine chelators are designed, and their supportive roles in the treatment of AD are further evaluated. The compounds have good multifunctional activities in the inhibition of acetylcholinesterase (Wang et al, 2019). Nano-N2PY, a NP-chelator conjugate, plays a significant role in protecting cortical neurons from Aβ-related toxicity (Liu et al, 2009a).…”

Section: Np-chelation-based Ad Therapymentioning

confidence: 99%

Nanomedicine: A Promising Way to Manage Alzheimer’s Disease

Khan

Mir

Ngowi

et al. 2021

Front. Bioeng. Biotechnol.

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Alzheimer’s disease (AD) is a devastating disease of the aging population characterized by the progressive and slow brain decay due to the formation of extracellular plaques in the hippocampus. AD cells encompass tangles of twisted strands of aggregated microtubule binding proteins surrounded by plaques. Delivering corresponding drugs in the brain to deal with these clinical pathologies, we face a naturally built strong, protective barrier between circulating blood and brain cells called the blood–brain barrier (BBB). Nanomedicines provide state-of-the-art alternative approaches to overcome the challenges in drug transport across the BBB. The current review presents the advances in the roles of nanomedicines in both the diagnosis and treatment of AD. We intend to provide an overview of how nanotechnology has revolutionized the approaches used to manage AD and highlight the current key bottlenecks and future perspective in this field. Furthermore, the emerging nanomedicines for managing brain diseases like AD could promote the booming growth of research and their clinical availability.

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Design, synthesis and evaluation of a novel metal chelator as multifunctional agents for the treatment of Alzheimer’s disease

Cited by 17 publications

References 41 publications

Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one

Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one

Mechanisms Involved in Microglial-Interceded Alzheimer’s Disease and Nanocarrier-Based Treatment Approaches

Nanomedicine: A Promising Way to Manage Alzheimer’s Disease

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