Identification of potential neuroprotective compound from <i>Ganoderma lucidum</i> extract targeting microtubule affinity regulation kinase 4 involved in Alzheimer's disease through molecular dynamics simulation and <scp>MMGBSA</scp>

Ahmad, Faizan; Singh, Gagandeep; Soni, Hemant; Tandon, Smriti

doi:10.1002/agm2.12232

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…et al; 2021 found out that irisin; (a protein that plays a vital role in memory dysfunction in AD) binds with MARK4 and maintains stability [30]. Most recent data indicates that ganoderic acid A and ganoderenic acid B are the most promising molecules derived from Ganoderma lucidium that bind with MARK4 [31]. Previous research supports our study, and ebelin lactone is considered the most promising neuroprotective compound from the Bacopa monnieri extract, which binds with MARK4.…”

Section: Discussionsupporting

confidence: 83%

Ebelin lactone as the most promising neuroprotective compound from Bacopa monnieri extract targeting microtubule affinity regulation kinase-4 involved in Alzheimer’s disease: A Computational Study

Ahmad

Abiha

Ahmad³

et al. 2023

Preprint

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Background Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which amyloid-beta (Aβ) and tau tangles are vital in causing neurodegeneration. Only five FDA-approved drugs are available in the market which manages the symptoms. In this study, 52 novel phytochemicals were selected from the medicinal plant Bacopa monnieri, a medicinal plant with neuroprotective compounds.Objective The main aim of this study is to find the most promising compound inhibiting microtubule affinity regulation kinase 4 (MARK 4), which is involved in AD.Methods First, an ADMET analysis was conducted, and the selected compounds were molecularly docked against the MARK4-associated protein (5ES1). Based on the top five binding affinities, a molecular dynamics simulation was performed.Results Cucurbitacin E, oroxindin, ebelin lactone, cucurbitacin B, and bacosine showed binding affinity of more than − 10.0 kcal/mol, and molecular dynamics (MD) simulations of these molecules in complex with MARK4 was performed. Subsequent trajectory analysis for structural changes and end-state MMGBSA binding energy were performed for Cucurbitacin E, oroxindin, ebelin lactone, cucurbitacin B and bacosine. The MD simulation and MMGBSA calculations showed stable interactions between the screened molecules and MARK4.Conclusion This computational study predicted ebelin lactone to be the most promising compound from Bacopa monnieri that can be further developed as a drug to treat AD after pre-clinical and clinical studies.

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Section: Discussionsupporting

confidence: 83%

Ebelin lactone as the most promising neuroprotective compound from Bacopa monnieri extract targeting microtubule affinity regulation kinase-4 involved in Alzheimer’s disease: A Computational Study

Ahmad

Abiha

Ahmad³

et al. 2023

Preprint

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“…Bacosides isolated from Brahmi, are non polar glycosides in nature and they easily cross the blood brain barrier [42][43][44]. This has been confirmed by radiopharmaceuticals biodistribution studies [45]. Thus, the Brahmi, rich in Bacosides have potent neuroprotective potentials and may be explored for utilizing the phytocompounds as lead molecules for developing more potent and effective neuroprotective drugs.…”

Section: Neuroprotective Compounds From Bacopa Monnieri (Brahmi)mentioning

confidence: 79%

Neuroprotective compounds from three common medicinal plants of West Bengal, India: a mini review

Ghosh,

Singha,

Ghosh

2023

Explor Neurosci

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Neural disorders refer to conditions of the nervous system due to infection or degeneration of the neurons leading to either neurodegenerative disorder or neuropsychiatric disorder. Some such disorders of the nervous system include Parkinsons’s disease, depression, amnesia, dementia, Alzheimer’s disease, schizophrenia, cerebrovascular impairment, epilepsy, seizure disorders, etc. In conventional medical system, some medicines belonging to the class of psychodelic drugs, sedatives, neurotransmitters, neuro-stimulants, etc. are in extensive use. Unfortunately, most of these drugs either delay the progression of the neural disorder or leave the patient with prominent adverse side effects. Several potent bioactive compounds with neuroprotective potential have been reported from medicinal plants and some of them have been found to be highly effective. Belonging from natural sources, mostly, the plant derived compounds exhibit minimum or no cytotoxicity at a prescribed standardised dose against a particular health ailment. Many such phytocompounds from plant sources with potent neuroprotective activities have been in use in Ayurvedacharya, Unani, and Chinese medicine for ages. The compounds if isolated chemically, modified to make more potent neuroprotective derivatives and utilised to make highly effective neuroprotective pharmaceutical formulations with minimum side effects, may open new revolutionary doorways in neuropharmacology. In this review, it has been briefly discussed about the neuroprotective compounds isolated from certain indigenous plants of West Bengal, India, and their mechanism of action.

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“…The user has provided a numerical reference [ 28 ]. According to recent investigations [ 29 ], the molecules ganoderic acid A and ganoderenic acid B, produced from Ganoderma lucidium, have shown significant potential in their interaction with MARK4. According to the latest investigation, galantamine has been identified as a potentially effective inhibitor for MARK 4 [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the most promising anti ‐ Depressant drug targeting Microtubule Affinity Receptor Kinase 4 involved in Alzheimer’s Disease through molecular docking and molecular dynamics simulation

Ahmad,

Zeyaullah,

AlShahrani

et al. 2024

PLoS ONE

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Alzheimer’s Disease (AD) is the prevailing type of neurodegenerative illness, characterised by the accumulation of amyloid beta plaques. The symptoms associated with AD are memory loss, emotional variability, and a decline in cognitive functioning. To date, the pharmaceuticals currently accessible in the marketplace are limited to symptom management. According to several research, antidepressants have demonstrated potential efficacy in the management of AD. In this particular investigation, a total of 24 anti-depressant medications were selected as ligands, while the Microtubule Affinity Receptor Kinase 4 (MARK4) protein was chosen as the focal point of our study. The selection of MARK4 was based on its known involvement in the advancement of AD and other types of malignancies, rendering it a highly prospective target for therapeutic interventions. The initial step involved doing ADMET analysis, which was subsequently followed by molecular docking of 24 drugs. This was succeeded by molecular dynamics simulation and molecular mechanics generalised Born surface area (MMGBSA) calculations. Upon conducting molecular docking experiments, it has been determined that the binding affinities observed fall within the range of -5.5 kcal/mol to -9.0 kcal/mol. In this study, we selected six anti-depressant compounds (CID ID ‐ 4184, 2771, 4205, 5533, 4543, and 2160) based on their binding affinities, which were determined to be -9.0, -8.7, -8.4, -8.3, -8.2, and -8.2, respectively. Molecular dynamics simulations were conducted for all six drugs, with donepezil serving as the control drug. Various analyses were performed, including basic analysis and post-trajectory analysis such as free energy landscape (FEL), polarizable continuum model (PCM), and MMGBSA calculations. Based on the findings from molecular dynamics simulations and the MMGBSA analysis, it can be inferred that citalopram and mirtazapine exhibit considerable potential as anti-depressant agents. Consequently, these compounds warrant further investigation through in vitro and in vivo investigations in the context of treating AD.

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Identification of potential neuroprotective compound from Ganoderma lucidum extract targeting microtubule affinity regulation kinase 4 involved in Alzheimer's disease through molecular dynamics simulation and MMGBSA

Cited by 7 publications

References 29 publications

Ebelin lactone as the most promising neuroprotective compound from Bacopa monnieri extract targeting microtubule affinity regulation kinase-4 involved in Alzheimer’s disease: A Computational Study

Ebelin lactone as the most promising neuroprotective compound from Bacopa monnieri extract targeting microtubule affinity regulation kinase-4 involved in Alzheimer’s disease: A Computational Study

Neuroprotective compounds from three common medicinal plants of West Bengal, India: a mini review

Exploring the most promising anti ‐ Depressant drug targeting Microtubule Affinity Receptor Kinase 4 involved in Alzheimer’s Disease through molecular docking and molecular dynamics simulation

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