Literature DB >> 30720268

Novel Deoxyvasicinone-Donepezil Hybrids as Potential Multitarget Drug Candidates for Alzheimer's Disease.

Hongtao Du1,2, Xinlian Liu1,3, Jusen Xie1,3, Fang Ma4.   

Abstract

In this study, we designed and synthesized a series of deoxyvasicinone-donepezil hybrids and determined whether they could be used as novel multitarget inhibitors for Alzheimer's disease. In vitro studies showed that most of the hybrids demonstrated moderate to potent inhibition of hAChE, BACE1, and Aβ1-42 aggregation. In particular, the hybrids 10a, 10d, 11a, and 11j exhibited excellent inhibitory activities against hAChE (IC50 = 56.14, 5.91, 3.29, and 8.65 nM, respectively), BACE1 (IC50 = 0.834, 0.167, 0.129, and 0.085 μM, respectively), and Aβ1-42 aggregation (IC50 = 13.26, 19.43, 9.26, and 5.41 μM, respectively). In addition, 10a and 11a exhibited very low cytotoxicity and showed remarkable neuroprotective activity against Aβ1-42-induced damage in SH-SY5Y cells.

Entities:  

Keywords:  Alzheimer’s disease; acetylcholinesterase; deoxyvasicinone; β-amyloid peptide; β-secretase

Mesh：

Substances：

Year:  2019        PMID： 30720268     DOI： 10.1021/acschemneuro.8b00699

Source DB:  PubMed          Journal:  ACS Chem Neurosci        ISSN： 1948-7193            Impact factor:   4.418


  7 in total

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Review 2.  Effects of Linkers and Substitutions on Multitarget Directed Ligands for Alzheimer's Diseases: Emerging Paradigms and Strategies.

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3.  Novel hydroxybenzylamine-deoxyvasicinone hybrids as anticholinesterase therapeutics for Alzheimer's disease.

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Journal:  Bioorg Med Chem       Date:  2021-07-14       Impact factor: 3.461

4.  Development of novel N-(6-methanesulfonyl-benzothiazol-2-yl)-3-(4-substituted-piperazin-1-yl)-propionamides with cholinesterase inhibition, anti-β-amyloid aggregation, neuroprotection and cognition enhancing properties for the therapy of Alzheimer's disease.

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Review 5.  Perspectives for New and More Efficient Multifunctional Ligands for Alzheimer's Disease Therapy.

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6.  Novel Coumarin-Pyridine Hybrids as Potent Multi-Target Directed Ligands Aiming at Symptoms of Alzheimer's Disease.

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7.  Design and Synthesis of Novel Hybrid 8-Hydroxy Quinoline-Indole Derivatives as Inhibitors of Aβ Self-Aggregation and Metal Chelation-Induced Aβ Aggregation.

Authors:  Suresh K Bowroju; Nirjal Mainali; Srinivas Ayyadevara; Narsimha R Penthala; Sesha Krishnamachari; Samuel Kakraba; Robert J Shmookler Reis; Peter A Crooks
Journal:  Molecules       Date:  2020-08-08       Impact factor: 4.411
  7 in total

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