Medicinal Chemistry Research

, Volume 28, Issue 10, pp 1704–1717 | Cite as

In silico screening of anticholinesterase alkaloids for cyclooxygenase-2 (COX-2) and matrix metalloproteinase 8 (MMP-8) inhibitory potentials as multi-target inhibitors of Alzheimer’s disease

  • Ahmed A. IsholaEmail author
  • Kayode E Adewole
Original Research


Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with yet no effective drug treatment; although several anticholinesterases are being used to offer relief from the symptoms of the disease. Recent studies have indicated that over-activation of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-8 (MMP-8) may cause neuronal death in the brain of AD subjects, suggesting that inhibition of COX-2 and MMP-8 may be of therapeutic value in the management of AD. Therefore, it is important and rational to investigate new agents with anticholinesterase, COX-2 and MMP-8 inhibitory activities. In this study, molecular docking study was performed with earlier identified anticholinesterase alkaloids to search for compounds with high affinity for COX-2 and MMP-8. Molecular docking was done using Blind Docking Server while ligand-protein molecular interaction of compounds with remarkable inhibitory characteristics against COX-2 and MMP-8 were viewed with PyMOL. Alkaloids with high binding affinity and remarkable binding interaction with the target proteins were subjected to drug likeness investigation based on absorption-distribution-metabolism-excretion (ADME) properties using the Swiss online ADME web tool. Nine alkaloids (haloxysterol A, haloxysterol B, haloxysterol C, haloxysterol D, sarcodine, isosarcodine, axillaridine A, sarsalignenone and voacangine hydroxyindolenine) showed high affinities for both COX-2 and MMP-8. Thus, this in silico study identified 9 orally drugable, anticholinesterase alkaloids with COX-2 and MMP-8 multi-target activities that could be studied further as agents against AD.


Alkaloids Anticholinesterase Cyclooxygenase Matrix metalloproteinase 8 Molecular docking 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Authors and Affiliations

  1. 1.Department of Biochemistry, Faculty of Life SciencesUniversity of IlorinIlorinNigeria
  2. 2.Department of Biochemistry, Faculty of Basic Medical SciencesUniversity of Medical SciencesOndo CityNigeria

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