Cited by 204Cholinesterase and Neurodegenerative DiseasesComputational Drug Discovery MethodsEnzyme function and inhibition

The discovery of potential acetylcholinesterase inhibitors: A combination of pharmacophore modeling, virtual screening, and molecular docking studies

Open access
Lu, Shin-Hua, Wu, Josephine W, Liu, Hsuan-Liang, Zhao, Jian-Hua, Liu, Kung-Tien, Chuang, Chih-Kuang, Lin, Hsin-Yi, Tsai, Wei-Bor +1 more·2011·Journal of Biomedical Science

Abstract

Background: Alzheimer's disease (AD) is the most common cause of dementia characterized by progressive cognitive impairment in the elderly people. The most dramatic abnormalities are those of the cholinergic system. Acetylcholinesterase (AChE) plays a key role in the regulation of the cholinergic system, and hence, inhibition of AChE has emerged as one of the most promising strategies for the treatment of AD. Methods: In this study, we suggest a workflow for the identification and prioritization of potential compounds targeted against AChE. In order to elucidate the essential structural features for AChE, three-dimensional pharmacophore models were constructed using Discovery Studio 2.5.5 (DS 2.5.5) program based on a set of known AChE inhibitors. Results: The best five-features pharmacophore model, which includes one hydrogen bond donor and four hydrophobic features, was generated from a training set of 62 compounds that yielded a correlation coefficient of R = 0.851 and a high prediction of fit values for a set of 26 test molecules with a correlation of R 2 = 0.830. Our pharmacophore model also has a high Güner-Henry score and enrichment factor. Virtual screening performed on the NCI database obtained new inhibitors which have the potential to inhibit AChE and to protect neurons from Aβ toxicity. The hit compounds were subsequently subjected to molecular docking and evaluated by consensus scoring function, which resulted in 9 compounds with high pharmacophore fit values and predicted biological activity scores. These compounds showed interactions with important residues at the active site. Conclusions: The information gained from this study may assist in the discovery of potential AChE inhibitors that are highly selective for its dual binding sites.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/1423-0127-18-8

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Acetylcholine depletion in the central nervous system is involved in the pathophysiology of Alzheimer's disease.

    “ACh depletion in the central nervous system has been involved in the pathophysiology noticed in AD [90]”
  • Allicin is a membrane-permeable compound that can enter cells easily and interact with cellular thiols such as glutathione or cysteine residues in proteins as well as enzymes containing reactive cysteine, and this may be the potential interpretation of allicin's toxicity.

    “Allicin is a membrane-permeable compound that can enter cells easily and interact with cellular thiols such as glutathione or cysteine residues in proteins [37,89,90] as well as enzymes containing reactive cysteine and this may be the potential interpretation of allicin’s toxicity [63].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Poptodorov K Luu T Hoffmann RD Langer T, Hoffmann RD In Methods and principles in Medicinal Chemistry, Pharmacophores and Pharmacophores Searches 2006 2 Germany: Wiley-VCH:Weinheim 17 47

Cited by

Sorted by citations

Authors
Lu, S.-H., Wu, J. W., Liu, H.-L., Zhao, J.-H., Liu, K.-T., Chuang, C.-K., Lin, H.-Y., Tsai, W.-B., & Ho, Y.
Affiliations
  • National Taipei University of Technology (TW)
  • Institute of Nuclear Energy Research (TW)
  • Fu Jen Catholic University (TW)
  • National Taiwan University (TW)
  • Taipei Medical University (TW)
Corresponding author
Liu, Hsuan-Liang
Venue
Journal of Biomedical Science
Published
2011-01-21
Volume
18
Issue
1
Pages
8-8
ISSN
  • 1021-7770 (ISSN-L)
  • 1423-0127
OpenAlex
W2126661983
Cited by
204
References
48
Citations by year
2026: 16 · 2025: 10 · 2024: 14 · 2023: 16 · 2022: 27 · 2021: 15 · 2020: 8 · 2019: 13 · 2018: 19 · 2017: 16 · 2016: 14 · 2015: 11 · 2014: 7 · 2013: 10 · 2012: 6
FWCI
5.85
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Biomedical Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Taipei Medical University Repository (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Science Council
  • Taipei Medical University
  • Institute of Nuclear Energy Research
  • National Taipei University of Technology
Topics
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
Keywords
acetylcholinesterase inhibitors, Alzheimer's disease, pharmacophore modeling, virtual screening, molecular docking, NCI database, amyloid-beta toxicity, cholinergic system, drug discovery
MeSH terms
Acetylcholinesterase, Alzheimer Disease, Cholinesterase Inhibitors, Humans, Models, Biological, Models, Molecular, Neurons, Databases, Factual, Amyloid beta-Protein Precursor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review