A review on the hybrids of hydroxycinnamic acid as multi-target-directed ligands against Alzheimer’s disease

Zhang, Xiao; He, Xian-Hui; Chen, Qiuhe; Lu, Junfeng; Rapposelli, Simona; Pi, Rongbiao

doi:10.1016/j.bmc.2017.12.042

Cited by 70 publications

(47 citation statements)

References 50 publications

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“…Although much evidence has emerged from pre‐clinical studies and observational studies on the positive health effects of HCAs, the evidence from clinical studies is still rather limited compared to other polyphenol classes, although a significant number of studies have been published over the past two decades. As coffee was suggested to be the main source of HCAs (and especially CGAs) in most adult cohorts, many clinical trials have investigated the role of CGAs in CVD, obesity and diabetes, brain disorders and cancers (several examples are summarized in Table ).…”

Section: Dietary Intake Of Hydroxycinnamic Acids and Associated Healtmentioning

confidence: 99%

“…HCAs are an important group of polyphenols tested in various studies as potent therapeutic agents against various human diseases . The most well‐known HCAs – CaA and FeA – were shown to have many pharmacological activities, including anti‐inflammatory, antioxidant and neuroprotective properties – all these being associated with an important potential role in the treatment of neurodegenerative conditions (especially Alzheimer's disease) . In the last few decades, numerous derivatives of these acids and other cinnamates have been synthesized to target successfully various cardiometabolic, neurodegenerative conditions and cancers .…”

Section: Mechanism Of Action Of Hydroxycinnamic Acids: Recent Advancesmentioning

confidence: 99%

“…42,81,116,117 The most well-known HCAs -CaA and FeA -were shown to have many pharmacological activities, including anti-inflammatory, antioxidant and neuroprotective properties -all these being associated with an important potential role in the treatment of neurodegenerative conditions (especially Alzheimer's disease). 80 In the last few decades, numerous derivatives of these acids and other cinnamates have been synthesized to target successfully various cardiometabolic, neurodegenerative conditions and cancers. [79][80][81]116,117 In the following paragraphs we aim to summarize the latest lessons learned from pre-clinical and clinical studies with CaA and FeA.…”

Section: Hcas As Antioxidant Agents (Ros Scavengers)mentioning

confidence: 99%

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Hydroxycinnamic acids and human health: recent advances

2019

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There is an urgent need to improve human diet globally. Compelling evidence gathered over the past several decades suggests that a suboptimal diet is associated with many chronic diseases and may be responsible for more deaths than any other risks worldwide. The main components in our diet that need higher intake are whole grains, fruit and vegetables, and nuts and seeds; all of these are important sources of dietary fiber and polyphenols. The health benefits of dietary fiber and polyphenols are also supported by several decades of valuable research. However, the conclusions drawn from interventional human trials are not straightforward and the action mechanisms in improving human health are not fully understood. Moreover, there is a great inter‐individual variation caused by different individual capabilities of processing, absorbing and using these compounds effectively. Data on the bioavailability and bioefficacy of hydroxycinnamic acids (HCAs) are limited when compared to other classes of polyphenols (e.g. anthocyanins). This review aims to summarize the latest research advances related to HCA bioavailability and their biological effects revealed by epidemiological data, pre‐clinical and clinical studies. Moreover, we aim to review the effects of HCAs on gut microbiota diversity and function and its respective influence on host health. © 2019 Society of Chemical Industry

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Section: Dietary Intake Of Hydroxycinnamic Acids and Associated Healtmentioning

confidence: 99%

Section: Mechanism Of Action Of Hydroxycinnamic Acids: Recent Advancesmentioning

confidence: 99%

Section: Hcas As Antioxidant Agents (Ros Scavengers)mentioning

confidence: 99%

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Hydroxycinnamic acids and human health: recent advances

2019

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“…Given that AD is a multifactor‐associated disease, in short future, multifunctional drugs, which produce the synergistic effect by regulating several therapeutic targets concurrently, might lead to a breakthrough in AD treatment. Other groups and our group have designed and synthesized a series of novel multifunctional compounds targeting BACE 1, Aβ, Cu 2+ metal ions and/or ROS production . An ideal sAD animal model might be the critical approach for the R&D of multifunctional anti‐AD drugs.…”

Section: Nhps: a Bridge Between Rodents And Humans?mentioning

confidence: 99%

Advance of sporadic Alzheimer's disease animal models

Zhang

Chen

Mak

et al. 2019

Medicinal Research Reviews

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Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disease. In the past decades, numbers of promising drug candidates showed significant anti‐AD effects in preclinical studies but failed in clinical trials. One of the major reasons might be the limitation of appropriate animal models for evaluating anti‐AD drugs. More than 95% of AD cases are sporadic AD (sAD). However, the anti‐AD drug candidates were mainly tested in the familial AD (fAD) animal models. The diversity between the sAD and fAD might lead to a high failure rate during the development of anti‐AD drugs. Therefore, an ideal sAD animal model is urgently needed for the development of anti‐AD drugs. Here, we summarized the available sAD animal models, including their methodology, pathologic features, and potential underlying mechanisms. The limitations of these sAD animal models and future trends in the field were also discussed.

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“…Cinnamic acid derivatives are often found in some plant species and have various pharmacological activities such as anti‐inflammatory, antioxidant, neuroprotective, and anti‐amyloid aggregation activities . Since the main pharmacological effects of these compounds may be useful in the treatment of AD, their hybrids, especially with anticholinesterase, are promising agents as multi‐target‐directed ligands (MTDLs) to treat AD . Recently, Wang et al reported cinnamamide–dibenzylamine hybrids A with potent neurogenic, antioxidant, cholinergic, and neuroprotective properties (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Novel cinnamic acid–tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study

Ghafary

Najafi

Mohammadi-Khanaposhtani

et al. 2018

Archiv der Pharmazie

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A novel series of cinnamic acid–tryptamine hybrids was designed, synthesized, and evaluated as cholinesterase inhibitors. Anticholinesterase assays showed that all of the synthesized compounds displayed a clearly selective inhibition of butyrylcholinesterase (BChE), but only a moderate inhibitory effect toward acetylcholinesterase (AChE) was detected. Among these cinnamic acid–tryptamine hybrids, compound 7d was found to be the most potent inhibitor of BChE with an IC50 value of 0.55 ± 0.04 μM. This compound showed a 14‐fold higher inhibitory potency than the standard drug donepezil (IC50 = 7.79 ± 0.81 μM) and inhibited BChE through a mixed‐type inhibition mode. Moreover, a docking study revealed that compound 7d binds to both the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of BChE. Also, compound 7d was evaluated against β‐secretase, which exhibited low activity (inhibition percentage: 38%).

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A review on the hybrids of hydroxycinnamic acid as multi-target-directed ligands against Alzheimer’s disease

Cited by 70 publications

References 50 publications

Hydroxycinnamic acids and human health: recent advances

Hydroxycinnamic acids and human health: recent advances

Advance of sporadic Alzheimer's disease animal models

Novel cinnamic acid–tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study

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