{
  "abstract": "Acute lymphoblastic leukemia (ALL) is an aggressive hematological malignancy that requires rapid therapeutic intervention. In this study, a series of oxindole-based derivatives ( 5a-t ) was designed, synthesized, and evaluated for antiproliferative activity. Initial single-dose screening at the NCI-DTP identified five compounds for full five-dose evaluation. Among these, compound 5t emerged as the most potent analogue, demonstrating broad antiproliferative activity across the NCI-60 panel with GI 50 (MG-MID) values ranging from 9.05–45.24 μM and exhibiting pronounced selectivity toward leukemia cell lines. Compound 5t showed superior cytotoxicity against CCRF-CEM cells while displaying markedly lower toxicity toward normal fibroblasts (BJ and MRC-5), yielding selectivity indices >17, thereby outperforming ibrutinib. Kinase profiling revealed that 5t functions as a multi-kinase inhibitor, potently targeting JAK3, VEGFR2, and FGFR1, with sustained inhibition observed at low micromolar concentrations. Mechanistic studies further demonstrated dose-dependent S-phase accumulation, accompanied by a slight increase in the G2/M DNA-content fraction in CCRF-CEM cells, accompanied by a near-complete shutdown of bulk RNA and DNA synthesis by the most potent analogue 5o . Complementary molecular modeling supported stable binding of 5t to JAK3 and VEGFR2, while in silico ADME predictions indicated favorable oral drug-like properties. Collectively, these findings identify as a viable candidate for further preclinical evaluation for the development of new therapeutic agents against ALL.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "Muhamad Mustafa"
    },
    {
      "name": "Aya Soudi"
    },
    {
      "name": "Petr Dzubak"
    },
    {
      "name": "Sona Gurska"
    },
    {
      "name": "Ivo Frydrych"
    },
    {
      "name": "Marian Hajduch"
    },
    {
      "name": "Burak Tüzün"
    },
    {
      "name": "Ibrahim Salem"
    },
    {
      "name": "Tarek Ibrahim"
    },
    {
      "name": "Michael Smietana"
    },
    {
      "name": "Jean-Yves Winum"
    },
    {
      "name": "Omar Aly"
    },
    {
      "name": "Taha F.S. Ali"
    },
    {
      "name": "El-Shimaa M.N. Abdelhafez"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b2z4an9tc177d.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ejmcr.2026.100376",
  "fulltext_url": null,
  "id": "b2z4an9tc177d",
  "issns": [
    "2772-4174"
  ],
  "landing_url": "https://hal.science/hal-05794570v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.chim"
    ],
    [
      "openalex",
      "1605|Synthesis and biological activity"
    ]
  ],
  "openalex": "W7220866492",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2772417426000555/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/b2z4an9tc177d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:54Z",
      "native_id": "hal-05794570",
      "source": "hal",
      "url": "https://hal.science/hal-05794570v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Synthesis and biological activity",
      "subfield": "organic"
    }
  ],
  "title": "“Design, Synthesis, and Biological Evaluation of Novel Oxindole-Based Derivatives as Potent and Selective Antileukemic Agents.”",
  "title_text": "“Design, Synthesis, and Biological Evaluation of Novel Oxindole-Based Derivatives as Potent and Selective Antileukemic Agents.”",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:54Z",
  "url": "https://research.draconitic.com/paper/b2z4an9tc177d",
  "venue": "European Journal of Medicinal Chemistry Reports",
  "versions": []
}