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Discovery of Novel Tacrine–Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer’s Disease

Based on a multitarget strategy, a series of novel tacrine-pyrimidone hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound 27g possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC50 = 51.1 nM; GSK-3 beta: IC50 = 89.3 nM) a...

In vivo Evaluation of a Newly Synthesized Acetylcholinesterase Inhibitor in a Transgenic Drosophila Model of Alzheimer’s Disease

Alzheimer's disease is a neurodegenerative disease characterized by disrupted memory, learning functions, reduced life expectancy, and locomotor dysfunction, as a result of the accumulation and aggregation of amyloid peptides that cause neuronal damage in neuronal circuits. In the current study, we exploited a transgenic Drosophila melanogaster line, expressing amyloid-beta peptides to investigate the efficacy of a newly synthesized acetylcholinesterase inhibitor, named XJP-1, as a potential ...

Novel inhibitors of AChE and Aβ aggregation with neuroprotective properties as lead compounds for the treatment of Alzheimer's disease

A series of sulfone analogs of donepezil were designed and synthesized as novel acetylcholinesterase (AChE) inhibitors with the potent inhibiting A0 aggregation and providing neuroprotective effects as potential modalities for Alzheimer's disease (AD). Most of the target compounds displayed effective inhibition of AChE, especially compound 24r which displayed powerful inhibitory activity (IC50 1/4 2.4 nM). Kinetic and docking studies indicated that compound 24r was a mixed-type inhibitor. Fur...

Development of p-Tau Differentiated Cell Model of Alzheimer’s Disease to Screen Novel Acetylcholinesterase Inhibitors

Alzheimer's disease (AD) is characterized by an initial accumulation of amyloid plaques and neurofibrillary tangles, along with the depletion of cholinergic markers. The currently available therapies for AD do not present any disease-modifying effects, with the available in vitro platforms to study either AD drug candidates or basic biology not fully recapitulating the main features of the disease or being extremely costly, such as iPSC-derived neurons. In the present work, we developed and v...

Recent advances on ISRU technologies and study of microgravity impact on blood cells for deep space exploration

The long-term solution to problems like overcrowding, fossil fuel depletion, climate change, and decreasing natural resource availability could be overcome through space colonization and human presence in space, as well as the exploitation of extraterrestrial natural resources. In keeping with this, the objective of this work is to analyze current advancements in technology development for deep space exploration and colonization made by our research team as well as by other organizations with...

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Prodotti recenti

Discovery of Novel Tacrine–Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer’s Disease

In vivo Evaluation of a Newly Synthesized Acetylcholinesterase Inhibitor in a Transgenic Drosophila Model of Alzheimer’s Disease

Novel inhibitors of AChE and Aβ aggregation with neuroprotective properties as lead compounds for the treatment of Alzheimer's disease

Development of p-Tau Differentiated Cell Model of Alzheimer’s Disease to Screen Novel Acetylcholinesterase Inhibitors

Recent advances on ISRU technologies and study of microgravity impact on blood cells for deep space exploration

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