Design, synthesis and evaluation of novel ferulic acid- O -alkylamine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease

Sang, Zhipei; Pan, Wanli; Wang, Keren; Ma, Qinge; Yu, Lintao; Yang, Yan; Bai, Ping; Leng, Chaoliang; Xu, Qian; Li, Xiaoqing; Tan, Zhenghuai; Liu, Wenmin

doi:10.1016/j.ejmech.2017.02.039

Cited by 88 publications

(48 citation statements)

References 26 publications

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“…Ferulic acid- O -alkylamines can be classified as MTDLs combining ferulic acid with N -benzylpiperidine fragment into single molecule 85 . The pharmacological assessment of this subset consisted of screening inhibition against Ee AChE, eq BChE, where some of the compounds were reevaluated on rat AChE, rat BChE, h AChE, and h BChE.…”

Section: Donepezil Derivatives With Antioxidant Propertiesmentioning

confidence: 99%

Profiling donepezil template into multipotent hybrids with antioxidant properties

Mezeiová

Špilovská

Nepovimová

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Alzheimer’s disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer’s disease.

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Section: Donepezil Derivatives With Antioxidant Propertiesmentioning

confidence: 99%

Profiling donepezil template into multipotent hybrids with antioxidant properties

Mezeiová

Špilovská

Nepovimová

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Compounds 4a–9d were synthesized according to previous reports (Liu et al, ; Sang et al, ). One of cinnamic amides ( 3a–3f ) (1 mmol), anhydrous K 2 CO 3 (0.68 g, 5 mmol) were added into a flask with 25 mL acetone as the solvent, stirred and refluxed for 45 min.…”

Section: Methodsmentioning

confidence: 99%

Structure–activity study of fluorine or chlorine‐substituted cinnamic acid derivatives with tertiary amine side chain in acetylcholinesterase and butyrylcholinesterase inhibition

Gao

Tang

Liu

et al. 2019

Drug Development Research

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In this study, a series of new fluorine or chlorine-substituted cinnamic acid derivatives that contain tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results show that almost all the derivatives containing tertiary amine side chain (compounds 4a-9d) exhibit moderate or potent activity in AChE inhibition. By contrast, their parent compounds (compounds 3a-3f) in the absence of tertiary amine moitery exhibit poor inhibitory activity against AChE. For the compounds containing pyrroline or piperidine side chain, the bioactivity in AChE inhibition is much intense than those containing N,N-diethylamino side chain. The chlorine or fluorine substituted position produces a significant effect on the bioactivity and selectivity in AChE inhibition. Most of the compounds that contain para-substituted fluorine or chlorine exhibit potent activity against AChE and poor activity against BChE, while ortho-substituted analogs show the opposite effect. It is worth noticing that the compounds containing N,N-diethylamino side chain are exceptions to this pattern. Among the newly synthesized compounds, compounds 6d are the most potent in AChE inhibition (IC 50 = 1.11 ± 0.08 μmol/L) with high selectivity for AChE over BChE (selectivity ratio: 46.58). An enzyme kinetic study of compounds 6d suggests it produces a mixed-type inhibitory effect in AChE. K E Y W O R D Scholinesterase inhibitors, cinnamic acid, halogen

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“…Compounds 33 and 34 also exhibited the inhibition (33.8% and 39.4% for 33 and 34) of Aβ aggregation (Ignasik et al, 2012). Sang et al (2017) carried out the synthesis of new molecules comprising phthalimide and 4-amino tetrahydrothienoquinoline. The reaction was done by direct alkylation of 37a-e with 36 and 38.…”

Section: Indanone Derivatives Having Aromatic and Heterocyclic Ringsmentioning

confidence: 99%

“…It also showed the ability to cross the BBB as well as less toxicity. Molecular modeling studies of compound 52 presented cation-π interaction, π-π interactions and hydrophobic interactions with BuChE but only hydrophobic interactions were observed with AChE which may be the reason for its selectivity for BuChE (Sang et al, 2017). Xu et al (2016) combined the pharmacophores of donepezil and ferulic acid to produce new hybrid molecules.…”

Section: Donepezil and Ferulic Acid Hybrid Moleculesmentioning

confidence: 99%

Donepezil: A review of the recent structural modifications and their impact on anti-Alzheimer activity

Mohsin

Ahmad

2020

Braz. J. Pharm. Sci.

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Design, synthesis and evaluation of novel ferulic acid- O -alkylamine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease

Cited by 88 publications

References 26 publications

Profiling donepezil template into multipotent hybrids with antioxidant properties

Profiling donepezil template into multipotent hybrids with antioxidant properties

Structure–activity study of fluorine or chlorine‐substituted cinnamic acid derivatives with tertiary amine side chain in acetylcholinesterase and butyrylcholinesterase inhibition

Donepezil: A review of the recent structural modifications and their impact on anti-Alzheimer activity

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