{
  "abstract": "This study aimed to develop new dihdropyrimidones based inhibitors to slow Parkinson's disease progression by targeting casein kinase CK1, CK2, and α-synuclein receptors. A series of hemiaminal ether-functionalized DHPMs (3a-3h) was synthesized through late-stage alkoxymethylation of dihydropyrimidones in high yields (up to 92%) and characterized by NMR and mass spectrometry. Initial screening of the synthesized compounds (3a-3h) through molecular docking predicted strong binding to CK1 (PDB: 6RCG, up to -8.9 kcal mol⁻¹), CK2 (PDB: 3NSZ, up to -10.3 kcal mol⁻¹), and potential to inhibit α-synuclein (ASN) aggregation in both native (3Q25) and mutant forms (1XQ8). Normal mode analysis (NMA) examined the structural flexibility of mutant α-synuclein (1XQ8), while docking analysis identified potential binding regions (C1-C5), including interactions involving Ser129. In vitro studies suggested significant potential of the synthesized compounds through CK2 inhibition (IC₅₀: 9.3 to 13.5 µM), ADP-Glo™ kinase activity (IC₅₀: 1.69-21.45 µM), and nitric oxide scavenging activity to assess their potential antioxidant effects. Among the synthesized derivatives, (R)-menthyloxymethyl DHPM (3h) exhibited the highest activity, with IC₅₀ values of 9.3, 1.69, and 6.0 µM, respectively. Favorable ADMET and pharmacokinetic profiles supported the synthesized DHPM (3a-3h) derivatives as promising leads for inhibiting kinase activity (CK1/CK2) and preventing ASN aggregation in Parkinson's disease.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, University of Education Lahore Pakistan.",
    "Institute of Chemistry, University of Sargodha Sargodha Pakistan humaira.yasmeen@uos.edu.pk.",
    "Department of Pharmacology, Faculty of Pharmacy, Riphah International University Islamabad Pakistan.",
    "H.E.J Research Institute of Chemistry, ICCBS, University of Karachi Karachi Pakistan.",
    "WHO Sub-office, DHDC, Aziz Bhatti Shaheed Teaching Hospital Gujrat Pakistan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hamza Wakeel"
    },
    {
      "affs": [
        1
      ],
      "name": "Shanza Munir"
    },
    {
      "affs": [
        1
      ],
      "name": "Humaira Yasmeen Gondal",
      "orcid": "0000-0001-9532-681X"
    },
    {
      "affs": [
        1
      ],
      "name": "Zain Maqsood Cheema"
    },
    {
      "affs": [
        2
      ],
      "name": "Aleena Muskan"
    },
    {
      "affs": [
        2
      ],
      "name": "Imran Malik"
    },
    {
      "affs": [
        1
      ],
      "name": "Muhammad Nisar"
    },
    {
      "affs": [
        3
      ],
      "name": "Hina Siddiqui",
      "orcid": "0000-0003-0432-2237"
    },
    {
      "affs": [
        4
      ],
      "name": "Sadaf Khaliq Sultan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1kpjp4rnnsfb1.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra06901k",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13725853/?tool=EBI",
  "id": "1kpjp4rnnsfb1",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13725853",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7225129100",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13725853/pdf/?tool=EBI",
  "pmcid": "PMC13725853",
  "pmid": "42974366",
  "published": "2026-11-02",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/1kpjp4rnnsfb1.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:51Z",
      "native_id": "PMC:PMC13725853",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13725853"
    },
    {
      "first_seen": "2026-11-04T15:20:47Z",
      "native_id": "MED:42974366",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42974366"
    },
    {
      "first_seen": "2026-11-05T12:22:18Z",
      "native_id": "PMC13725853",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6ra06901k"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "New hemiaminal ether dihydropyrimidinones as CK1/CK2 inhibitors targeting α-synuclein in Parkinson's disease",
  "title_text": "New hemiaminal ether dihydropyrimidinones as CK1/CK2 inhibitors targeting α-synuclein in Parkinson's disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:56Z",
  "url": "https://research.draconitic.com/paper/1kpjp4rnnsfb1",
  "venue": "RSC advances",
  "versions": []
}