Synthesis, antioxidant and Aβ anti-aggregation properties of new ferulic, caffeic and lipoic acid derivatives obtained by the Ugi four-component reaction

Benchekroun, Mohamed; Pachón-Angona, Irène; Luzet, Vincent; Martin, Hélène; Oset-Gasque, María Jesús; Marco‐Contelles, José; Ismaïli, Lhassane

doi:10.1016/j.bioorg.2018.12.029

Cited by 21 publications

(14 citation statements)

References 24 publications

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“…Out of the 12 synthesized derivatives compounds 3 and 4 were found to be potent antioxidant agents with promising Aβ self-aggregation inhibition (Figure 5). Compound 3 also displayed neuroprotective action against peroxide induced cell damage in addition to Aβ inhibition (Benchekroun et al, 2019). Kikugawa et al inspected the effects of ferulic acid and its water-soluble derivatives 1-feruloyl glycerol, 1-feruloyl diglycerol against nitric oxide production and expression of inducible nitric oxide synthase in primary astrocytes of rats (Figure 6).…”

Section: Derivatives Of Ferulic Acid and Their Activit Ymentioning

confidence: 99%

Therapeutic potential of ferulic acid and its derivatives in Alzheimer’s disease—A systematic review

2021

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily caused by accumulation of amyloid-beta (Aβ) peptide extracellularly and neurofibrillary tangles intracellularly. Recently, it has been shown that oxidative stress and mitochondrial dysregulation play an important role in pathology of AD. Therefore, modulating various targets such as Aβ aggregation, neuro-inflammation, and oxidative stress, genetic factors such as Apolipoprotein E gene (ApoE) are some of the ways to manage AD. Studying the natural products which can act as multifunctional agents could be key toward discovering new therapeutics. Ferulic acid (FA) represents one such natural product, which has exhibited great potential in this regard.Found in the plant cell walls, FA is an antioxidant, free radical scavenger with antiinflammatory activity. Taking this into consideration, over the years, various derivatives have been reported as anti-AD molecules based on structure of FA. The present review explores the role of FA and its derivatives as therapeutic agents in AD.

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Section: Derivatives Of Ferulic Acid and Their Activit Ymentioning

confidence: 99%

Therapeutic potential of ferulic acid and its derivatives in Alzheimer’s disease—A systematic review

2021

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“…In addition, as shown as the equation (27) in Figure 9, caffeic acid ( 136 ) takes parts in the Ugi 4CR with benzylamine ( 97 ), benzyl isocyanide ( 130 ), and 2‐chloro‐3‐quinolinecarboxaldehyde ( 137 ) to afford a dipeptide ( 138 ) with high ability to suppress the amyloid‐β aggregation. This example emphasizes the importance of steric configuration for a molecule playing antioxidative role in a biological environment [47] …”

Section: Ugi and Passerini Reactionsmentioning

confidence: 94%

“…This example emphasizes the importance of steric configuration for a molecule playing antioxidative role in a biological environment. [47]…”

Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 99%

Multicomponent Reactions for Integrating Multiple Functional Groups into an Antioxidant

Liu

2020

The Chemical Record

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A large number of convincing evidences has revealed the correlation of the pathogeny of diseases with the oxidative damages of DNA, protein, biomembrane, and other biological species, while supplementation of antioxidants is demonstrated to be a promising way to avoid, at least, rectify the unbalance redox status in vivo. Although many endeavors have focused on synthesis of antioxidants, a main hurdle still hinders the wide usages of synthetic antioxidants because of low bioavailability and potential cytotoxicity. The search for antioxidants with multiple functional groups being recognized by different receptors becomes a much sought by researchers, and multicomponent reactions (MCRs) provide with powerful tools for the construction of multifunctional antioxidants. Presented herein is a personal account on the application of MCRs for the synthesis of multifunctional antioxidants, while radical-induced oxidation of DNA acts as the experimental system for evaluating antioxidative effect. Concretely, the Biginelli three-component reaction (3CR) affords such a dihydropyrimidine scaffold that the tautomerization between C=S and CÀ SH leads to antioxidative effect. The Povarov 3CR is able to integrate multiple antioxidative groups, i. e., ferrocenyl and À N(CH 3) 2 , into a quinoline scaffold, while the Groebke 3CR provides with imidazo[1,2-a]pyridine skeleton for inhibiting DNA oxidation. Additionally, the Knoevenagel-related MCRs also become efficient strategies for achieving radical-scavengers. On the other hand, the Ugi 4CR and Passerini 3CR result in the dipeptide and α-acyloxycarboxamide, respectively, with the benefit for the integration of antioxidative features by aliphatic chains. Therefore, MCRs have emerged as efficient tools for integrating multiple antioxidative features into one molecule in order to meet with complicated requirements from various biological surroundings.

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“…[10] Based on the above evidence, we have prepared a library of novel Tacrine-based MTSMs as AChE inhibitors, showing neuroprotective effect and strong antioxidant activity. [11][12][13] Herein we report the design, synthesis and biological evaluation of a new family of tacrine derivatives 2,4-diaryl-6,7,8,9-tetrahydropyrimido [4,5-b]quinolin-5-amines. These new compounds (Figure 2) result from the juxtaposition of a pyrimidine scaffold as antioxidant [14,15] and tacrine.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Assessment of PyrimidoTacrines as Promising Agents for Alzheimer's Disease Therapy

Dakhlaoui

Maalej²,

Martin

et al. 2021

ChemistrySelect

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Considering the multifactorial nature of Alzheimer's disease (AD), multitarget small molecules (MTSMs) represent the most potent and attractive therapeutic strategy to design new drugs for Alzheimer's disease therapy. Thus, new Pyrimidotacrines were designed and synthesized by merging pyrimidine scaffold and tacrine. Among them, 4-(4-nitrophenyl)-2-phenyl-6,7,8,9tetrahydropyrimido[4,5-b]quinolin-5-amine (4 j) was identified as less hepatotoxic than tacrine at high concentration, a submicromolar inhibitor against both acetylcholinesterase (AChE) (IC 50 = 677 � 28 nM) and butyrylcholinesterase (BuChE) (IC 50 = 756 � 41 nM) showing potent antioxidant properties (2.43 TE) and displaying a strong neuroprotection effect against hydrogen peroxide (H 2 O 2 ) and Oligomycin Rotenone. Consequently, 4 j is a potential new hit-ligand for AD therapy for further biological exploration[a] I.

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Synthesis, antioxidant and Aβ anti-aggregation properties of new ferulic, caffeic and lipoic acid derivatives obtained by the Ugi four-component reaction

Cited by 21 publications

References 24 publications

Therapeutic potential of ferulic acid and its derivatives in Alzheimer’s disease—A systematic review

Therapeutic potential of ferulic acid and its derivatives in Alzheimer’s disease—A systematic review

Multicomponent Reactions for Integrating Multiple Functional Groups into an Antioxidant

Synthesis and Biological Assessment of PyrimidoTacrines as Promising Agents for Alzheimer's Disease Therapy

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