{
  "abstract": "Identifying acetylcholinesterase (AChE) ligands for Alzheimer’s disease research requires integrating molecular recognition with pharmacokinetic and safety considerations. Here, four designed chromone derivatives (M1–M4) were investigated to determine how conformational sampling and complementary molecular descriptors refine docking-based prioritization. Donepezil redocking in human AChE and cross-docking into Torpedo californica AChE recovered the crystallographic and transferred reference orientations, respectively, with RMSDs of 0.942 and 1.074 Å. Molecular docking was integrated with 800 ns molecular dynamics, MM/PBSA, electronic-structure calculations, and pharmacokinetic/toxicity predictions. M4 achieved the most favorable chromone docking score (−9.6 kcal mol−1), whereas M3 yielded the most favorable chromone MM/PBSA estimate within the 775–800 ns window (−23.90 ± 2.31 kcal mol−1). Donepezil retained a more favorable MM/PBSA estimate (−41.00 ± 2.75 kcal mol−1). M4 exhibited the highest electronic hardness, while predicted toxicity profiles revealed distinct liabilities across the series. The divergence between docking and sampled energetics highlights the value of integrating complementary criteria when selecting compounds for experimental evaluation. These protocol-dependent findings prioritize M3 and M4 as complementary computational candidates requiring experimental confirmation of AChE inhibition, selectivity, and safety.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Materials Chemistry and Applications (LCMA), Department of Chemistry, Faculty of Sciences, Mohammed Premier University, BP 717, Oujda 60000, Morocco",
    "Laboratory of Physical Chemistry of Materials, Natural Substances and Environment, Chemistry Department, Faculty of Sciences and Techniques of Tangier, Tangier 90090, Morocco",
    "Biological Engineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Mghila, P.O. Box 523, Beni Mellal 23000, Morocco",
    "Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia",
    "BioSTM—UR 7537 Biostatistics, Processing and Modelling of Biological Data, Université Paris Cité, 75006 Paris, France"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Oussama Khibech",
      "orcid": "0009-0007-9407-7576"
    },
    {
      "affs": [
        1
      ],
      "name": "Bahia Abdelfattah",
      "orcid": "0009-0008-8311-2513"
    },
    {
      "affs": [
        2
      ],
      "name": "Mohamed Bouhrim",
      "orcid": "0000-0001-9944-811X"
    },
    {
      "affs": [
        3
      ],
      "name": "Moneerah J. Alqahtani",
      "orcid": "0000-0003-3013-1354"
    },
    {
      "affs": [
        3
      ],
      "name": "Jawaher H. Alqahtani",
      "orcid": "0000-0002-3640-9612"
    },
    {
      "affs": [
        4
      ],
      "name": "Joe Miantezila Basilua",
      "orcid": "0000-0002-5658-9382"
    },
    {
      "affs": [
        0
      ],
      "name": "Aziz Boulouiz"
    },
    {
      "affs": [
        0
      ],
      "name": "Rachid Touzani",
      "orcid": "0000-0001-7333-697X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a0rbxv9n1wa6y.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209153",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705499/?tool=EBI",
  "id": "a0rbxv9n1wa6y",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9153",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2736|Cholinesterase and Neurodegenerative Diseases"
    ]
  ],
  "openalex": "W7222153089",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705499/pdf/?tool=EBI",
  "pmcid": "PMC13705499",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/a0rbxv9n1wa6y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27209153",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9153"
    },
    {
      "first_seen": "2026-10-30T12:21:44Z",
      "native_id": "PMC:PMC13705499",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705499"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Cholinesterase and Neurodegenerative Diseases",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Multiscale Computational Prioritization of Chromone-Based Acetylcholinesterase Ligands",
  "title_text": "Multiscale Computational Prioritization of Chromone-Based Acetylcholinesterase Ligands",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:44Z",
  "url": "https://research.draconitic.com/paper/a0rbxv9n1wa6y",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}