{
  "abstract": "Pancreatic cancer remains one of the most lethal malignancies, with limited therapeutic options and high chemoresistance partly associated with β-tubulin overexpression. In this study, we synthesized and biologically evaluated a series of 4-thiazolidinone derivatives, identifying Les-6666 and Les-5549 as potent anticancer candidates. An optimized microwave-assisted synthetic protocol enabled efficient and environmentally friendly production of selected derivatives. In silico ADMET profiling predicted favorable drug-like properties, high gastrointestinal absorption, and no blood–brain barrier penetration. Molecular docking studies revealed strong binding affinity of selected compounds to the colchicine and combretastatin A4 (CA4) sites of β-tubulin. Biological evaluation through the NCI-60 screening program demonstrated pronounced antiproliferative activity, with Les-6666 exhibiting submicromolar GI50 values across multiple cancer cell lines. In pancreatic MIA PaCa-2 cells, both Les-6666 and Les-5549 showed potent cytotoxicity (IC50 = 0.08 μM and 0.10 μM, respectively), inhibited DNA synthesis, suppressed clonogenic survival, reduced migration, arrested cells at the G2/M phase of the cell cycle and induced apoptosis. Tubulin polymerization assays confirmed significant depolymerizing activity comparable to CA4. Furthermore, Les-6666 reduced β-tubulin protein expression, consistent with tubulin autoregulatory feedback mechanisms. Collectively, these findings identify Les-6666 as a promising antiproliferative agent that inhibits tubulin polymerization in pancreatic cancer cells warranting further investigation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "Rostyslav Dudchak"
    },
    {
      "name": "Serhii Holota"
    },
    {
      "name": "Magdalena Podolak"
    },
    {
      "name": "Olga Klaudia Szewczyk-Roszczenko"
    },
    {
      "name": "Ihor Yushyn"
    },
    {
      "name": "Nazar Solodyak"
    },
    {
      "name": "Olexandr Karpenko"
    },
    {
      "name": "Robert Czarnomysy"
    },
    {
      "name": "Agnieszka Gornowicz"
    },
    {
      "name": "Małgorzata Borzym-Kluczyk"
    },
    {
      "name": "Yegor Vassetzky"
    },
    {
      "name": "Anna Bielawska"
    },
    {
      "name": "Krzysztof Bielawski"
    },
    {
      "name": "Roman Lesyk"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9p7sm073ewnsy.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bioorg.2026.110149",
  "fulltext_url": null,
  "id": "9p7sm073ewnsy",
  "issns": [
    "0045-2068",
    "1090-2120"
  ],
  "landing_url": "https://hal.science/hal-05760420v1",
  "language": "en",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1605|Synthesis and biological activity"
    ]
  ],
  "openalex": "W7165536333",
  "pdf_url": "https://hal.science/hal-05760420/document",
  "pmcid": null,
  "pmid": "42341571",
  "published": "2026-06-22",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/9p7sm073ewnsy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:39Z",
      "native_id": "hal-05760420",
      "source": "hal",
      "url": "https://hal.science/hal-05760420v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Synthesis and biological activity",
      "subfield": "organic"
    }
  ],
  "title": "Targeting microtubule dynamics: synthesis and evaluation of novel 4-thiazolidinone derivatives in pancreatic Cancer",
  "title_text": "Targeting microtubule dynamics: synthesis and evaluation of novel 4-thiazolidinone derivatives in pancreatic Cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:39Z",
  "url": "https://research.draconitic.com/paper/9p7sm073ewnsy",
  "venue": "Bioorganic Chemistry",
  "versions": []
}