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Identification of potential inhibitors of cholinergic and β-secretase enzymes from phytochemicals derived from Gongronema latifolium Benth leaf: an integrated computational analysis

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Abstract

Neurodegenerative disorders (NDDs) are associated with increased activities of the brain acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-secretase enzyme (BACE1). Inhibition of these enzymes affords therapeutic option for managing NDDs such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Although, Gongronema latifolium Benth (GL) has been widely documented in ethnopharmacological and scientific reports for the management of NDDs, there is paucity of information on its underlying mechanism and neurotherapeutic constituents. Herein, 152 previously reported Gongronema latifolium derived-phytochemicals (GLDP) were screened against hAChE, hBChE and hBACE-1 using molecular docking, molecular dynamics (MD) simulations, free energy of binding calculations and cluster analysis. The result of the computational analysis identified silymarin, alpha-amyrin and teraxeron with the highest binding energies (-12.3, -11.2, -10.5 Kcal/mol) for hAChE, hBChE and hBACE-1 respectively as compared with those of the reference inhibitors (-12.3, -9.8 and − 9.4 for donepezil, propidium and aminoquinoline compound respectively). These best docked phytochemicals were found to be orientated in the hydrophobic gorge where they interacted with the choline-binding pocket in the A-site and P-site of the cholinesterase and subsites S1, S3, S3’ and flip (67–75) residues of the pocket of the BACE-1. The best docked phytochemicals complexed with the target proteins were stable in a 100 ns molecular dynamic simulation. The interactions with the catalytic residues were preserved during the simulation as observed from the MMGBSA decomposition and cluster analyses. The presence of these phytocompounds most notably silymarin, which demonstrated dual high binding tendencies to both cholinesterases, were identified as potential neurotherapeutics subject to further investigation.

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Data Availability

All data generated or analysed during this study are included in this published article [and its supplementary information files].

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science and Technology, P.M.B 005, Karu, Nasarawa State, Nigeria

    Gideon Ampoma Gyebi & Gabriel O. Anyanwu

  2. Natural Products and Structural (Bio-Chem)-informatics Research Laboratory (NpsBC-Rl), Bingham University, Nasarawa, Nigeria

    Gideon Ampoma Gyebi

  3. Nutritional and Industrial Biochemistry Unit, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria

    Oludare M. Ogunyemi

  4. Department of Biophysics, Faculty of Sciences, Cairo University, Giza, Egypt

    Ibrahim M. Ibrahim

  5. Department of Biological Sciences, KolaDaisi University, Ibadan, Nigeria

    Olalekan B. Ogunro

  6. Faculty of Basic Medical Sciences, Department of Pharmacology and Therapeutics, University of Ilorin, Ilorin, Nigeria

    Saheed O. Afolabi

  7. Department of Biochemistry, Faculty of Computing and Applied Sciences, Baze University, Abuja, Nigeria

    Rotimi J. Ojo

  8. Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira, 22511, Egypt

    Gaber El-Saber Batiha

  9. Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin, Nigeria

    Joseph O. Adebayo

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  1. Gideon Ampoma Gyebi
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  2. Oludare M. Ogunyemi
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  4. Olalekan B. Ogunro
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  5. Saheed O. Afolabi
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  8. Gaber El-Saber Batiha
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  9. Joseph O. Adebayo
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Contributions

Conceptualization: Gideon A. Gyebi; Methodology: Gideon A. Gyebi, Oludare M. Ogunyemi, Ibrahim M. Ibrahim; Formal analysis and investigation: Gideon A. Gyebi; Writing - original draft preparation: Gideon (A) Gyebi; Writing - review and editing: Olalekan (B) Ogunro, Saheed O. Afolabi, Gabriel O. Anyanwu, Ibrahim M. Ibrahim, Rotimi J. Ojo; Resources: Gaber El-Saber Batiha; Supervision: Joseph O. Adebayo.

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Correspondence to Gideon Ampoma Gyebi.

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Gyebi, G.A., Ogunyemi, O.M., Ibrahim, I.M. et al. Identification of potential inhibitors of cholinergic and β-secretase enzymes from phytochemicals derived from Gongronema latifolium Benth leaf: an integrated computational analysis. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10658-y

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