Medicinal Chemistry Research

, Volume 26, Issue 11, pp 2768–2784 | Cite as

Docking-based comparative intermolecular contacts analysis and in silico screening reveal new potent acetylcholinesterase inhibitors

  • Maha Habash
  • Sawsan Abuhamdah
  • Khaled Younis
  • Mutasem O. TahaEmail author
Original Research


The positive impact of acetylcholinesterase enzyme inhibitors on neurodegenerative diseases impelled continuous attempts to discover and optimize new acetylcholinesterase enzyme inhibitors. The combined recent interest inacetylcholinesterase enzyme inhibitors, together with known shortages of docking and docking validation methods prompted us to use our new 3D-QSAR method, namely, docking-based comparative intermolecular contacts analysis, to identify optimal docking conditions required to dock certain group of inhibitors into acetylcholinesterase enzyme binding site. Additionally, optimal docking-based comparative intermolecular contacts analysis models were converted into pharmacophore models, which were validated by receiver operating characteristic curve analysis. The pharmacophores were subsequently used as search queries to mine the national cancer institute list of compounds for new acetylcholinesterase enzyme inhibitors. Five low micromolar acetylcholinesterase enzyme inhibitors were identified. The most potent gave IC50 value of 2.55 μM.


Acetylcholinesterase Docking-based Comparative Intermolecular Contacts Analysis Libdock virtual screening 



This project was sponsored by the Deanship of Scientific Research at the University of Jordan. The authors wish to thank the National Cancer Institute for freely providing hit compounds for experimental validation.

Compliance with ethical standards

Conflict of Interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1976_MOESM1_ESM.doc (2.9 mb)
Supplementary Information


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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Pharmaceutics and Pharmaceutical Sciences, Faculty of PharmacyAqaba University of TechnologyAqabaJordan
  2. 2.Department of Biopharmaceutics and Clinical Pharmacy, Faculty of PharmacyUniversity of JordanAmmanJordan
  3. 3.Department of Computer Engineering, Faculty of EngineeringUniversity of JordanAmmanJordan
  4. 4.Drug Discovery Unit, Department of Pharmaceutical Sciences, Faculty of PharmacyUniversity of JordanAmmanJordan

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