Rapid neurobehavioural analysis based on the effects of an acetylcholinesterase inhibitor from Tephrosia purpurea in Zebrafish

Kannan, Rajaretinam Rajesh; Vincent, Samuel Gnana Prakash

doi:10.5214/ans.0972.7531.180403

Cited by 9 publications

(4 citation statements)

References 25 publications

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“…Several neuroactive compounds like piracetam, methylenedioxymethamphetamine, hallucinogenic agents like mescaline and phencyclidine, a nitroamine explosive 1,3,5-Trinitroperhydro-1,3,5-triazine, kynurenic acid, Δ 9 -tetrahydrocannabinol and heroin (diacetylmorphine) have been tested using zebrafish 178 – 184 . Rapid behaviour-based screening has also evolved as an inexpensive assay for identifying small neuroactive molecules 130 , 185 .…”

Section: Neurospecific Drug Discovery Using Zebrafish Modelmentioning

confidence: 99%

Zebrafish: an emerging real-time model system to study Alzheimer’s disease and neurospecific drug discovery

2018

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Zebrafish (Danio rerio) is emerging as an increasingly successful model for translational research on human neurological disorders. In this review, we appraise the high degree of neurological and behavioural resemblance of zebrafish with humans. It is highly validated as a powerful vertebrate model for investigating human neurodegenerative diseases. The neuroanatomic and neurochemical pathways of zebrafish brain exhibit a profound resemblance with the human brain. Physiological, emotional and social behavioural pattern similarities between them have also been well established. Interestingly, zebrafish models have been used successfully to simulate the pathology of Alzheimer’s disease (AD) as well as Tauopathy. Their relatively simple nervous system and the optical transparency of the embryos permit real-time neurological imaging. Here, we further elaborate on the use of recent real-time imaging techniques to obtain vital insights into the neurodegeneration that occurs in AD. Zebrafish is adeptly suitable for Ca2+ imaging, which provides a better understanding of neuronal activity and axonal dystrophy in a non-invasive manner. Three-dimensional imaging in zebrafish is a rapidly evolving technique, which allows the visualisation of the whole organism for an elaborate in vivo functional and neurophysiological analysis in disease condition. Suitability to high-throughput screening and similarity with humans makes zebrafish an excellent model for screening neurospecific compounds. Thus, the zebrafish model can be pivotal in bridging the gap from the bench to the bedside. This fish is becoming an increasingly successful model to understand AD with further scope for investigation in neurodevelopment and neurodegeneration, which promises exciting research opportunities in the future.

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Section: Neurospecific Drug Discovery Using Zebrafish Modelmentioning

confidence: 99%

Zebrafish: an emerging real-time model system to study Alzheimer’s disease and neurospecific drug discovery

2018

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“…These compounds were designed from the trans -tephrostachin. It was isolated and structuraly characterized from Tephrosia purpurea in our previous studies [ 25 , 26 , 27 ]. To investigate the mechanism of trans -tephrostachin derivatives against AChE, kinetic studies were conducted for all compounds.…”

Section: Resultsmentioning

confidence: 99%

“…Flavonoids have been reported to be attractive natural products that are widely available in nature and have strong biological activity. We have identified AChE inhibitory flavonoid trans -tephrostachin from the herbal Tephrosia purpurea [ 25 , 26 , 27 ]. Therefore, the compounds of trans -tephrostachin and derivatives were designed and synthesized, for anti-AD drug development.…”

Section: Introductionmentioning

confidence: 99%

Molecular interaction of human acetylcholinesterase with trans-tephrostachin and derivatives for Alzheimer's disease

Pitchai

Kannan

Rajasekar

et al. 2020

Heliyon

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Alzheimer's disease (AD), a neurodegenerative disorder affects more than 35 million people globally. Acetylcholinesterase suppression is the common approach to enhance the well-being of AD patients by increasing the duration of acetylcholine in the cholinergic synapses. Generally, herbal secondary metabolites are reported to be a major resource for acetylcholinesterase inhibitors (AChEIs). Trans-tephrostachin was reported from Tephrosia purpurea for AChE inhibition. Here, we report on the design, synthesis, and assessment of human acetylcholinesterase inhibitory activity from trans-tephrostachin derivatives or analogs as anti-AD agents. The five newly synthesized compounds 4a. 4b, 4c, 4d and 4e displayed potent inhibitory activities with IC 50 values of 35.0, 35.6, 10.6, 10.3, and 28.1 μM respectively. AChE enzyme kinetic study was performed for the five derived compounds using the Ellman's method. The Lineweaver-Burk and the secondary plots revealed the mixed inhibition for 4a, 4c and 4d whereas 4b and 4e demonstrated competitive inhibition. Molecular docking and molecular dynamics simulations showed the derivatives or analogs of trans-tephrostachin attained a high binding affinity and efficacy than the standard drug. In conclusion, trans-tephrostachin and its derivative compounds could become effective agents for further drug development to treat AD.

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“…Acetylcholinesterase (AChE) (E.С.3.1.1.7) is a serine hydrolase which catalyzes the hydrolysis of neurotransmitter acetylcholine into choline and acetic acid [ 1 , 2 ]. According to cholinergic neurotransmission, acetylcholinesterase (AChE) inhibition would increase the levels of acetylcholine in the brain, thus improving cholinergic synapses in Alzheimer’s disease (AD) patients [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Natural Peptides in Drug Discovery Targeting Acetylcholinesterase

Prasasty

Radifar²,

Istyastono

2018

Molecules

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Acetylcholinesterase-inhibitory peptide has gained much importance since it can inhibit acetylcholinesterase (AChE) and increase the availability of acetylcholine in cholinergic synapses, enhancing cholinergic transmission in pharmacological treatment of Alzheimer’s disease (AD). Natural peptides have received considerable attention as biologically important substances as a source of AChE inhibitors. These natural peptides have high potential pharmaceutical and medicinal values due to their bioactivities as neuroprotective and neurodegenerative treatment activities. These peptides have attracted great interest in the pharmaceutical industries, in order to design potential peptides for use in the prophylactic and therapy purposes. Some natural peptides and their derivatives have high commercial values and have succeeded in reaching the pharmaceutical market. A large number of peptides are already in preclinical and clinical pipelines for treatment of various diseases. This review highlights the recent researches on the various natural peptides and future prospects for AD management.

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Rapid neurobehavioural analysis based on the effects of an acetylcholinesterase inhibitor from Tephrosia purpurea in Zebrafish

Cited by 9 publications

References 25 publications

Zebrafish: an emerging real-time model system to study Alzheimer’s disease and neurospecific drug discovery

Zebrafish: an emerging real-time model system to study Alzheimer’s disease and neurospecific drug discovery

Molecular interaction of human acetylcholinesterase with trans-tephrostachin and derivatives for Alzheimer's disease

Natural Peptides in Drug Discovery Targeting Acetylcholinesterase

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