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Dioxinodehydroeckol: A Potential Neuroprotective Marine Compound Identified by In Silico Screening for the Treatment and Management of Multiple Brain Disorders

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Abstract

Neurodegenerative disorders such as Alzheimer’s disease (AD), Glioblastoma multiforme (GBM), Amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD) are some of the most prevalent neurodegenerative disorders in humans. Even after a variety of advanced therapies, prognosis of all these disorders is not favorable, with survival rates of 14–20 months only. To further improve the prognosis of these disorders, it is imperative to discover new compounds which will target effector proteins involved in these disorders. In this study, we have focused on in silico screening of marine compounds against multiple target proteins involved in AD, GBM, ALS, and PD. Fifty marine-origin compounds were selected from literature, out of which, thirty compounds passed ADMET parameters. Ligand docking was performed after ADMET analysis for AD, GBM, ALS, and PD-associated proteins in which four protein targets Keap1, Ephrin A2, JAK3 Kinase domain, and METTL3-METTL14 N6-methyladenosine methyltransferase (MTA70) were found to be binding strongly with the screened compound Dioxinodehydroeckol (DHE). Molecular dynamics simulations were performed at 100 ns with triplicate runs to validate the docking score and assess the dynamics of DHE interactions with each target protein. The results indicated Dioxinodehydroeckol, a novel marine compound, to be a putative inhibitor among all the screened molecules, which might be effective against multiple target proteins involved in neurological disorders, requiring further in vitro and in vivo validations.

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Data Availability

The authors state that the data generated to reach the conclusion of this article are included in the article.

Abbreviations

Aβ:

Amyloid beta

Ach:

Acetylcholine

AD:

Alzheimer’s Disease

ALS:

Amyotrophic lateral sclerosis

APOE4:

Apolipoprotein E4

APP:

Amyloid precursor protein

BBB:

Blood: Brain Barrier

CNS:

Central Nervous System

CADD:

Computer: aided drug design

DHE:

Dioxinodehydroeckol

GBM:

Glioblastoma multiforme

GO:

Gene Ontology

LRRK2:

Leucine-rich repeat kinase 2

NMDA:

N-methyl D-aspartate

NIST:

National Institute of Standards and Technology

PD:

Parkinson’s Disease

RMSD:

Root Mean Square Deviation

RMSF:

Root mean square fluctuation

SSE:

Secondary structural elements

TMZ:

Temozolomide

TYK2:

Tyrosine kinase 2

VEGFR:

Vascular endothelial growth factor receptor

WHO:

World Health Organization

ZFD:

Zinc Finger Domain

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Acknowledgements

The authors would like to acknowledge Mr. Muhammad Nasir Iqbal for providing the simulation facility and Mr. Nobendu Mukherjee for analyzing the MD results and assisting in article formatting.

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Author notes

  1. Faizan Ahmad and Gagandeep Singh have contributed equally.

Authors and Affiliations

  1. Department of Medical Elementology and Toxicology, Jamia Hamdard University, Delhi, India

    Faizan Ahmad

  2. Amity Institute of Neuropsychology and Neurosciences, Amity University, Noida, Uttar Pradesh, India

    Punya Sachdeva

  3. Department of Physics and Astrophysics, University of Delhi, Delhi, India

    Bhuvi Sachdeva

  4. Section of Microbiology, Central Ayurveda Research Institute, CCRAS, Ministry of AYUSH, Jhansi, India

    Gagandeep Singh, Hemant Soni & Smriti Tandon

  5. Kusuma School of Biological Sciences, India Institute of Technology, Delhi, India

    Gagandeep Singh

  6. Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia

    Misbahuddin M. Rafeeq

  7. Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia

    Mohammad Zubair Alam

  8. Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

    Mohammad Zubair Alam

  9. Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia

    Hanadi M. Baeissa

  10. Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj, 11942, Saudi Arabia

    Mohammad Khalid

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  1. Faizan Ahmad
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Contributions

FA and GS helped in writing the manuscript and idea generation; PS, BS, HS, and ST helped in writing the manuscript; MMR, MZA, HMB, and MK helped in revision and editing of the manuscript.

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Correspondence to Faizan Ahmad.

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Ahmad, F., Sachdeva, P., Sachdeva, B. et al. Dioxinodehydroeckol: A Potential Neuroprotective Marine Compound Identified by In Silico Screening for the Treatment and Management of Multiple Brain Disorders. Mol Biotechnol 66, 663–686 (2024). https://doi.org/10.1007/s12033-022-00629-3

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