Design, synthesis and biological evaluation of D-ring opened galantamine analogs as multifunctional anti-Alzheimer agents

Fang, Lei; Fang, Xubin; Gou, Shaohua; Lupp, Amelie; Lenhardt, Isabell; Sun, Yanyan; Huang, Zhangjian; Chen, Yao; Zhang, Yihua; Fleck, Christian

doi:10.1016/j.ejmech.2014.02.035

Cited by 57 publications

(23 citation statements)

References 29 publications

(36 reference statements)

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“…The charges and force field parameters of A01-04 were derived from antechamber 32,33) and the in general Amber force field (GAFF). 32) Ligand charges of A01-04 were +1, +1, +1, and +2, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-Aβ Aggregation Activity through Molecular Docking-Based Virtual Screening

Liu

Jiao

Lin

et al. 2020

CHEMICAL & PHARMACEUTICAL BULLETIN

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Discovery of novel multifunctional inhibitors targeting acetylcholinesterase (AChE) has becoming a hot spot in anti-Alzheimer's disease (AD) drug development. In the present study, four potent small molecule inhibitors (A01, A02, A03 and A04) of AChE with new chemical scaffold were identified. Inhibitor A03 displayed the most potent inhibition activity on AChE at enzymatic level with IC 50 value of 180 nM, and high selectivity towards AChE over butyrylcholinesterase (BChE) by more than 100-fold. The binding modes of compounds A01-A04 were carefully analyzed by molecular docking and molecular dynamics (MD) simulation to provide informative clues for further structure modification. Finally, the anti-amyloid beta (Aβ) aggregation and neuroprotective activity were also well investigated. Our findings highlighted the therapeutic promise of AChE inhibitors A01-A04 for AD treatment.

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Section: Methodsmentioning

confidence: 99%

“…Anti-Aβ 1-42 Aggregation Bioassay The compounds' anti-Aβ 1-42 aggregation potency was determined by using ThT-based fluorometric assay method. 34) The detailed protocol was included in Supplementary Materials.…”

Section: Methodsmentioning

confidence: 99%

Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-Aβ Aggregation Activity through Molecular Docking-Based Virtual Screening

Liu

Jiao

Lin

et al. 2020

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Among these compounds, analog III (Fig. ) showed a potent inhibition activity toward AChE . According to these reports, the carbazole scaffold emerges as attractive building block in the search of new agents to confront AD.…”

Section: Introductionmentioning

confidence: 97%

“…Moreover, the substituted carbazole derivative carvedilol ( II ) was an effective inhibitor of Aβ fibril formation . Recently, Fang et al described a series of carbazole derivatives, which can be considered as the d ‐ring opened analogs of galantamine ( I ). Among these compounds, analog III (Fig.…”

Section: Introductionmentioning

confidence: 99%

9H‐Carbazole Derivatives Containing the N‐Benzyl‐1,2,3‐triazole Moiety as New Acetylcholinesterase Inhibitors

Akrami

Mirjalili

Khoobi

et al. 2015

Archiv der Pharmazie

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A series of triazole-containing carbazole derivatives were designed as new anti-acetylcholinesterase (AChE) agents. The target compounds 6a-q were simply prepared via a one-pot three-component click reaction of N-propargyl-9H-carbazole, sodium azide, and an appropriate benzyl halide. The in vitro anti-cholinesterase assay showed that the unsubstituted benzyl derivative 6p along with the 2-F, 2-Me, 3-Me, 3-MeO, and 3-F analogs (6a, 6c, and 6g-i) had significant anti-AChE activity (IC50s ≤ 3.8 μM). Among them, the 2-methylbenzyl derivative 6c with an IC50 value of 1.9 μM was the most active compound. The SAR studies revealed that small halogen atoms such as the fluorine atom or electron-donating groups such as methyl or methoxy at the ortho or meta positions of the benzyl pendent group could be tolerated or improved the anti-AChE activity.

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“…In order to overcome limitations of the scope and to avoid undesired side reactions, such as hydrodediazonation, numerous attempts to find improved conditions have been undertaken over the decades, e.g. by using hydroquinone or copper salts as promoters. Photoredox catalysis , although highly successful for promoting many free radical transformations of the Pschorr type, has been of limited use in the case of dibenzofuran synthesis .…”

Section: Introductionmentioning

confidence: 99%

Microwave‐Promoted Pd‐Catalyzed Synthesis of Dibenzofurans from Ortho‐Arylphenols

Schmidt

Riemer

2016

Journal of Heterocyclic Chem

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Design, synthesis and biological evaluation of D-ring opened galantamine analogs as multifunctional anti-Alzheimer agents

Cited by 57 publications

References 29 publications

Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-Aβ Aggregation Activity through Molecular Docking-Based Virtual Screening

Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-Aβ Aggregation Activity through Molecular Docking-Based Virtual Screening

9H‐Carbazole Derivatives Containing the N‐Benzyl‐1,2,3‐triazole Moiety as New Acetylcholinesterase Inhibitors

Microwave‐Promoted Pd‐Catalyzed Synthesis of Dibenzofurans from Ortho‐Arylphenols

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