{
  "abstract": "In the present study, a series of novel 6,8-dibromo-7-hydroxy-4-methylcoumarin-cyanoacrylate hybrids and their corresponding pyrazole derivatives were designed, synthesized, and evaluated for antiproliferative activity against breast cancer cells. Among the tested compounds, cyanoacrylate derivative 8 emerged as the most active analogue against MCF-7 cells (IC₅₀ = 5.9 ± 0.4 µM) and retained antiproliferative activity against MDA-MB-231 cells (IC₅₀ = 11.7 ± 0.4 µM). Compound 8 exhibited weaker cytotoxicity toward the non-cancerous MCF-10A and WI-38 cell lines (IC₅₀ = 46 ± 3 and 37.4 ± 1.3 µM, respectively), although the magnitude of selectivity was cell-context dependent. Mechanistic investigations in MCF-7 cells revealed pronounced G2/M cell-cycle arrest (7.57% to 32.24%), inhibition of tubulin polymerization (IC₅₀ = 4.7 ± 0.2 µM), and EGFR kinase activity (IC₅₀ = 50 ± 3 nM). Flow-cytometric analysis showed an increase in total apoptotic cells from 2.71% to 33.19%, while LDH release increased 2.88-fold, indicating concomitant loss of membrane integrity. qRT-PCR demonstrated upregulation of BAX (7.9-fold), caspase-9 (8.8-fold), and p53 (4.7-fold) and downregulation of BCL-2 (0.27-fold), with corresponding protein-level changes confirmed by ELISA, providing complementary evidence for activation of the intrinsic apoptotic pathway. Molecular docking provided structural hypotheses for potential interactions of compound 8 within the tubulin colchicine-binding region and EGFR ATP-binding site. In vivo, compound 8 significantly suppressed tumor burden in the Ehrlich ascites carcinoma (EAC) mouse model, reducing viable tumor-cell counts by up to 72.4% and ascitic tumor volume by 85.3%. Treatment also ameliorated tumor-associated hepatic and renal dysfunction, oxidative stress, and inflammatory alterations, with histopathological and immunohistochemical findings supporting tissue recovery. Collectively, these findings identify compound 8 as a promising antiproliferative and antitumor lead and support further optimization and evaluation of this scaffold in more clinically relevant breast cancer models.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, Faculty of Science, Port Said University Port Said Egypt m.elzend@sci.psu.edu.eg ieldeen@yahoo.com Zeinab.elsayed@sci.psu.edu.eg.",
    "Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University Makkah 21955 Saudi Arabia imanzi@uqu.edu.sa.",
    "Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University P.O. Box 84428 Riyadh 11671 Saudi Arabia SZAlshawwa@pnu.edu.sa.",
    "Chemistry Department, Faculty of Science, Suez Canal University Ismailia 41522 Egypt essa.saied@science.suez.edu.eg.",
    "Institute for Chemistry, Humboldt Universität zu Berlin 12489 Berlin Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Manar A El-Zend",
      "orcid": "0000-0001-9957-2188"
    },
    {
      "affs": [
        0
      ],
      "name": "Ibrahim M El-Deen"
    },
    {
      "affs": [
        0
      ],
      "name": "Zeinab Abdelkarim"
    },
    {
      "affs": [
        1
      ],
      "name": "Ibrahim M Alanazi",
      "orcid": "0000-0003-4865-7215"
    },
    {
      "affs": [
        2
      ],
      "name": "Samar Zuhair Alshawwa",
      "orcid": "0000-0001-9232-7956"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Essa M Saied",
      "orcid": "0000-0002-7342-6200"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3a68bce2r7my3.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra06101j",
  "fulltext_url": "https://europepmc.org/articles/PMC13712327",
  "id": "3a68bce2r7my3",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948722",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "1605|Synthesis and biological activity"
    ]
  ],
  "openalex": "W7223791483",
  "pdf_url": "https://europepmc.org/articles/PMC13712327?pdf=render",
  "pmcid": "PMC13712327",
  "pmid": "42948722",
  "published": "2026-10-27",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/3a68bce2r7my3.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:33Z",
      "native_id": "MED:42948722",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948722"
    },
    {
      "first_seen": "2026-10-31T12:22:56Z",
      "native_id": "PMC13712327",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6ra06101j"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Synthesis and biological activity",
      "subfield": "organic"
    }
  ],
  "title": "Development of 7-hydroxy-4-methylcoumarin-cyanoacrylate hybrids with antiproliferative activity against breast cancer cells: from molecular design to in vivo validation.",
  "title_text": "Development of 7-hydroxy-4-methylcoumarin-cyanoacrylate hybrids with antiproliferative activity against breast cancer cells: from molecular design to in vivo validation.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:56Z",
  "url": "https://research.draconitic.com/paper/3a68bce2r7my3",
  "venue": "RSC advances",
  "versions": []
}