Molecules, Vol. 25, Pages 985: Design, Synthesis, and In Vitro Evaluation of Hydroxybenzimidazole-Donepezil Analogues as Multitarget-Directed Ligands for the Treatment of Alzheimer ’s Disease

Molecules, Vol. 25, Pages 985: Design, Synthesis, and In Vitro Evaluation of Hydroxybenzimidazole-Donepezil Analogues as Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease Molecules doi: 10.3390/molecules25040985 Authors: Chaves Resta Rinaldo Costa Josselin Gwizdala Piemontese Capriati Pereira-Santos Cardoso Santos : A series of multi-target-directed ligands (MTDLs), obtained by attachment of a hydroxyphenylbenzimidazole (BIM) unit to donepezil (DNP) active mimetic moiety (benzyl-piperidine/-piperazine) was designed, synthesized, and evaluated as potential anti-Alzheimer’s disease (AD) drugs in terms of biological activity (inhibition of acetylcholinesterase (AChE) and β–amyloid (Aβ) aggregation), metal chelation, and neuroprotection capacity. Among the DNP-BIM hybrids studied herein, the structural isomerization did not significantly improve the biological properties, while some substitutions, namely fluorine atom in each moiety or the methoxy group in the benzyl ring, evidenced higher cholinergic AChE activity. All the compounds are able to chelate Cu and Zn metal ions through their bidentate BIM moieties, but compound 5, containing a three-dentate chelating unit, is the strongest Cu(II) chelator. Concerning the viability on neuroblastoma cells, compounds 9 and 10 displayed the highest reduction of Aβ-induced cell toxicity. In silico calculations of some pharmacoki...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research

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In conclusion, this study shows that P‐tau can modulate AChE expression and it suggests that AChE may possibly increase in the initial phases of AD.
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Original Article Source Type: research
In conclusion, this study shows that P‐tau can modulate AChE expression and it suggests that AChE may possibly increase in the initial phases of AD.
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research
CONCLUSION: These compounds have potential to serve as a dual binding site inhibitor and might provide a useful template for the development of new anti- Alzheimer's disease agents. PMID: 32888280 [PubMed - as supplied by publisher]
Source: CNS and Neurological Disorders Drug Targets - Category: Drugs & Pharmacology Authors: Tags: CNS Neurol Disord Drug Targets Source Type: research
Dimethyl Fumarate Exerts Neuroprotection by Modulating Calcineurin/NFAT1 and NFκB Dependent BACE1 Activity in a Neuronal Model of Alzheimer's Disease. Brain Res Bull. 2020 Aug 30;: Authors: Rajput MS, Nirmal NP, Rathore D, Dahima R Abstract Ample studies signify a key part of calcineurin, a Ca2+/calmodulin-sensitive phosphatase in Alzheimer's disease beginning and/or clinical progression and alteration of calcineurin has been confirmed in the Alzheimer's disease brain, impacting tau proteins and amyloid beta (Aβ) levels and resulting in neuronal cell death. As, it is sensible to deliberate ...
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research
Dimethyl Fumarate Mitigates Tauopathy in Aβ-Induced Neuroblastoma SH-SY5Y Cells. Neurochem Res. 2020 Aug 20;: Authors: Rajput MS, Nirmal NP, Rathore D, Dahima R Abstract Alzheimer's disease pathogenesis is measured by two key hallmarks viz extracellular senile plaques composed of insoluble amyloid beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau, resulting in microtubule destabilization, synaptic damage and neurodegeneration. Accumulation of Aβ is an introducing pathological incident in Alzheimer's disease; hence, the effect of dimethyl fumarate (DMF) on Aβ...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
Alzheimer ’s disease (AD) is a progressive neuro-degenerative disease with a major manifestation of dementia. MicroRNAs were reported to regulate the transcript expression in patients with Alzheimer’s disease (...
Source: BMC Neuroscience - Category: Neuroscience Authors: Tags: Research article Source Type: research
Scouting around 1,2,3,4-Tetrahydrochromeno[3,2-c]pyridin-10-ones for Single- and Multi-target Ligands Directed towards Relevant Alzheimer's Targets. ChemMedChem. 2020 Jul 27;: Authors: Purgatorio R, Kulikova L, Pisani L, Catto M, de Candia M, Carrieri A, Cellamare S, De Palma A, Beloglazkin A, Raesi GR, Voskressensky L, Altomare CD Abstract A number of 1,2,3,4-tetrahydrochromeno[3,2-c]pyridin-10-one derivatives were synthesized and screened against different targets involved in Alzheimer's Disease (AD) onset and progression, such as acetyl- and butyrylcholinesterase (AChE and BChE), monoamine oxi...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research
In conclusion, our findings confirmed that miR-29c-3p attenuated Aβ-induced neurotoxicity through regulation of NF-κB signaling pathway by directly targeting TNFAIP1, providing the potential value for the treatment of AD patients. PMID: 32712875 [PubMed - as supplied by publisher]
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
Low Levels of Brain-Derived Neurotrophic Factor Trigger Self-aggregated Amyloid β-Induced Neuronal Cell Death in an Alzheimer's Cell Model. Biol Pharm Bull. 2020;43(7):1073-1080 Authors: Tagai N, Tanaka A, Sato A, Uchiumi F, Tanuma SI Abstract Alzheimer's disease (AD) is pathologically characterized by accumulation of amyloid β (Aβ) and hyperphosphorylated tau, and thereby induction of neuronal cell death. The Aβ-induced neuronal cell death has been shown to occur by several modes, such as apoptosis, necrosis, and necroptosis. Interestingly, in AD patients, the brain and serum leve...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research
The common MRI technique called T1 mapping -- typically used for patients with...Read more on AuntMinnie.comRelated Reading: Imaging shows new, post-SARS-CoV-2 illness in children Preop MRI finds 11% more cancer in women with DCIS PET, MRI uncover women's predisposition to Alzheimer's Imaging reveals baby girl in SC born with 2nd mouth Caution indicated with new GBCAs for kidney patients
Source: AuntMinnie.com Headlines - Category: Radiology Source Type: news
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