{
  "abstract": "3,4-Dihydropyrimidin-2(1H)-ones (DHPMs) are privileged heterocyclic scaffolds with broad biological activities. Sixteen DHPM hybrids (4a–p) carrying para- or ortho-aryloxy linkers and diverse terminal amines were prepared through a modular propargylation, Mannich-type, and Biginelli sequence. The compounds were ranked by NIH/3T3 cytotoxicity, MCF-7 antiproliferative activity (SRB assay), and colony formation under continuous exposure at the MCF-7 IC25. Compounds 4a and 4m were the most potent in MCF-7 cells (IC50 = 10.7 and 11.6 µM; preliminary selectivity indices of 9.6 and 9.1), but 4m inhibited colony formation by 68.3% compared with 25.3% for 4a, supporting its prioritization as the most balanced lead. Ligand-based target prediction followed by GNINA screening of seven candidate targets identified TOP2A as the best match to the experimental pIC50 ranking (Pearson r = 0.883, Spearman ρ = 0.893, n = 7), with Eg5/KIF11 as a secondary comparator. Docking, 200 ns molecular dynamics, and MM/PBSA estimates were compatible with this hypothesis but did not constitute experimental target validation. These data identify 4m as a starting point for DHPM-based antiproliferative agents and TOP2A as a hypothesis to be tested experimentally.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, Faculty of Science, Al-Balqa Applied University, P.O. Box 206, Al-Salt 19117, Jordan",
    "Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy",
    "Department of Chemistry, Faculty of Science, The Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan",
    "Department of Chemical Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy",
    "Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D’Alcontres 31, 98166 Messina, Italy"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hadeel D. Sultan"
    },
    {
      "affs": [
        1
      ],
      "name": "Rocco Buccheri",
      "orcid": "0009-0005-8966-0439"
    },
    {
      "affs": [
        0
      ],
      "name": "Anas J. Rasras",
      "orcid": "0000-0003-4203-7031"
    },
    {
      "affs": [
        0
      ],
      "name": "Mohammad S. Alzubi",
      "orcid": "0009-0000-7772-542X"
    },
    {
      "affs": [
        2
      ],
      "name": "Eyad A. Younes",
      "orcid": "0000-0001-6892-2077"
    },
    {
      "affs": [
        3
      ],
      "name": "Placido Mineo",
      "orcid": "0000-0003-3382-9272"
    },
    {
      "affs": [
        4
      ],
      "name": "Maria S. Molonia"
    },
    {
      "affs": [
        4
      ],
      "name": "Francesco Cimino",
      "orcid": "0000-0002-8954-4797"
    },
    {
      "affs": [
        1
      ],
      "name": "Antonio Rescifina",
      "orcid": "0000-0001-5039-2151"
    },
    {
      "affs": [
        4
      ],
      "name": "Nicola Micale",
      "orcid": "0000-0002-9294-6033"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/69nny0d4f0a2s.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219618",
  "fulltext_url": null,
  "id": "69nny0d4f0a2s",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9618",
  "language": null,
  "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",
      "1605|Synthesis and biological activity"
    ]
  ],
  "openalex": "W7223989692",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/69nny0d4f0a2s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219618",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9618"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Synthesis and biological activity",
      "subfield": "organic"
    }
  ],
  "title": "3,4-Dihydropyrimidin-2(1H)-one Hybrids as Phenotypic Anti-Breast Cancer Agents: Synthesis, Colony-Formation Profiling and Computational Target Deconvolution",
  "title_text": "3,4-Dihydropyrimidin-2(1H)-one Hybrids as Phenotypic Anti-Breast Cancer Agents: Synthesis, Colony-Formation Profiling and Computational Target Deconvolution",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/69nny0d4f0a2s",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}