Design, synthesis and evaluation of chromone-2-carboxamido-alkylbenzylamines as multifunctional agents for the treatment of Alzheimer’s disease

Liu, Qiang; Qiang, Xiaoming; Li, Yan; Sang, Zhipei; Li, Yuxing; Tan, Zhenghuai; Deng, Yong

doi:10.1016/j.bmc.2015.01.042

Cited by 49 publications

(12 citation statements)

References 42 publications

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“…6 In particular, the approach of designing multitarget agents against neurodegenerative diseases has shown an increase. [7][8][9] For example, recent reports include multifunctional agent chromone-2-carboxyamidoalkylbenzylamines 10 and tacrine-8-hydroxyquinoline hybrids. 11 Both groups of compounds target the cholinesterase enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), act as chelating agent with copper ion and inhibit Aβ aggregation.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

et al. 2019

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Section: Introductionmentioning

confidence: 99%

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

et al. 2019

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“…23,60 However, a noteworthy feature of this study is that both the present systems, with the slightest substitution in the chromone moiety, exhibit an inhibitory efficacy comparable and, even in some cases, greater than other generously substituted chromone derivatives reported in the literature. 17-19,21…”

Section: Discussionmentioning

confidence: 99%

“…In this context, several 3-formylchromone derivatives, with very promising AChE inhibitory activities, have been synthesized by Parveen et al 17 Through a multi-target-directed ligand strategy, some chromone-based compounds have been synthesized which can exhibit plural biologically relevant activities. 18 Novel chromones like 2-carboxamidoalkylbenzylamines have been developed by Liu et al 19 as AChE inhibitors showing inhibitory efficiency in the sub-micromolar concentration range (the lowest with IC 50 = 0.07 μM), with some compounds possessing higher selectivity for AChE over butyl cholinesterase (BuChE). These compounds also demonstrated perceptible inhibition of the aggregation of amyloid-β (Aβ) fibrils through self- as well as Cu 2+ -induction, another important pathway in the hypothesis of AD.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potency of substituted chromones as Alzheimer’s drug: Elucidation of acetylcholinesterase inhibitory activity through spectroscopic and molecular modelling investigation

et al. 2019

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Introduction: Documentation on the potency of chromones as acetylcholinesterase (AChE) antagonists has paved the way for the design and usage of new chromone analogues as inhibitors of AChE modelled on the hypothesis based on cholinergic pathway of Alzheimer’s disease (AD). Here, 2 minimally substituted chromones, namely 3-cyanochromone (CyC) and 7-amino-3-methylchromone (AMC), were checked for their AChE inhibition efficacies and plasma protein modulation. Methods: Colorimetric enzymatic assay as well as fluorescence measurements were performed for obtaining the experimental results, which were further corroborated by molecular docking and simulation studies. Results: The investigated systems exhibited strong inhibition activities against AChE, with CyC (IC50= 85.12 ± 6.70 nM) acting as better inhibitor than AMC (IC50 = 103.09 ± 11.90 nM) and both having IC50 values in the range of FDA approved cholinergic drug Donepezil (IC50 = 74.13 ± 8.30 nM). Non-competitive inhibition was observed in both the cases with the inhibitors binding near the peripheral anionic site (PAS) of the enzyme. Having one planar nitrile group in CyC as compared to sp3 hybridised substituents in AMC facilitated stacking interactions in the former, accounting for its higher inhibitory efficacy. A significant decrease in the inhibition potency of CyC (~32%) was noted in comparison with AMC (~5%) when the experiments were performed in presence of human serum albumin (HSA) instead of pure aqueous buffer. Conclusion: This comparative study affirms the importance of meticulous substitution in the chromone scaffold to promote maximum inhibition potency, while considering their usage as AD drugs.

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“…Chromone scaffold ((4H)-1-benzopyran-4-one) has also been extensively recognized as a key pharmacophore [ 207 - 214 ]. The chromone ring is the core fragment of several flavonoid derivatives, such as flavones and isoflavones [ 215 ]. The structural diversity of chromones in nature allows their division into simple and fused chromones.…”

Section: Chromone Derivativesmentioning

confidence: 99%

From Hybrids to New Scaffolds: The Latest Medicinal Chemistry Goals in Multi-target Directed Ligands for Alzheimer’s Disease

Alarcón-Espósito

Mallea

Rodríguez-Lavado

2021

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: Alzheimer’s disease (AD) is a chronic, progressive, and fatal neurodegenerative disorder affecting cognition, behavior, and function, being one of the most common causes of mental deterioration in elderly people. Once thought as being just developed because of β amyloid depositions or neurofibrillary Tau tangles, during the last decades, numerous ADrelated targets have been established, the multifactorial nature of AD became evident. In this context, the one drug-one target paradigm has resulted to be inefficient in facing AD and other disorders with complex etiology, opening the field for the emergence of the multitarget approach. In this review, we highlight the recent advances within this area, emphasizing in hybridization tools of well-known chemical scaffolds endowed with pharmacological properties concerning AD, such as curcumin-, resveratrol-, chromone- and indole-. We focus mainly on well stablished and incipient AD therapeutic targets, AChE, BuChE, MAOs, β-amyloid deposition, 5-HT4 and Serotonin transporter, with the aim to shed light about new insights in the AD multitarget therapy.

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Design, synthesis and evaluation of chromone-2-carboxamido-alkylbenzylamines as multifunctional agents for the treatment of Alzheimer’s disease

Cited by 49 publications

References 42 publications

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

Therapeutic potency of substituted chromones as Alzheimer’s drug: Elucidation of acetylcholinesterase inhibitory activity through spectroscopic and molecular modelling investigation

From Hybrids to New Scaffolds: The Latest Medicinal Chemistry Goals in Multi-target Directed Ligands for Alzheimer’s Disease

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