{
  "abstract": "KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) is characterized by a high mortality that still lacks efficient therapies. Monoketone-based bisarylidene curcuminoid derivatives have shown promising activities against various PDAC models. Based on our previous findings on anticancer-active N-acryloyl-modified piperidin-4-one derivatives, we replaced the reactive acryloyl moiety by a series of N-arylsulfonyl bis-difluoro/trifluoromethylbenzylidene piperidin-4-one derivatives and tested them for antiproliferative activity against KRAS-mutant PDAC cells. Furthermore, apoptosis induction based on caspase-3/7 activation and STAT3 inhibition were investigated for the most promising compound. Notably, the N-tosyl derivative 3a with 4-trifluoromethyl substituents at the benzylidene rings exhibited the highest antiproliferative activities against PDAC cells (IC50 = 0.22–0.26 µM, 48 h). Derivative 3a also strongly induced apoptosis in PDAC cells and suppressed STAT3 activation/phosphorylation, which was supported by molecular docking of this curcuminoid into the SH2 domain of STAT3 and by 3a-STAT3 binding confirmed using CETSA in MiaPaCa-2 cells. These findings identify compound 3a as a promising lead for further preclinical evaluation in KRAS-mutant PDAC models and in other STAT3-dependent cancer types.",
  "abstract_shown": true,
  "affiliations": [
    "Cancer Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA",
    "Organic Chemistry 1, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hindole Ghosh"
    },
    {
      "affs": [
        0
      ],
      "name": "Duha Qamar Azaz"
    },
    {
      "affs": [
        0
      ],
      "name": "Addhyan Saxena",
      "orcid": "0009-0009-9426-0893"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicole Bodenhausen"
    },
    {
      "affs": [
        1
      ],
      "name": "Rainer Schobert",
      "orcid": "0000-0002-8413-4342"
    },
    {
      "affs": [
        1
      ],
      "name": "Bernhard Biersack",
      "orcid": "0000-0001-7305-346X"
    },
    {
      "affs": [
        0
      ],
      "name": "Prasad Dandawate",
      "orcid": "0000-0002-1141-3703"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/63x730jfaa6jf.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms272110013",
  "fulltext_url": null,
  "id": "63x730jfaa6jf",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/10013",
  "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": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-08",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/63x730jfaa6jf.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:39Z",
      "native_id": "10.3390/ijms272110013",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/10013"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Activity of Fluoro-Substituted 3,5-Di[(E)-Benzylidene]piperidin-4-Ones with N-Arylsulfonyl Appendages Against KRAS-Mutant Pancreatic Ductal Adenocarcinoma Cells",
  "title_text": "Activity of Fluoro-Substituted 3,5-Di[(E)-Benzylidene]piperidin-4-Ones with N-Arylsulfonyl Appendages Against KRAS-Mutant Pancreatic Ductal Adenocarcinoma Cells",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:39Z",
  "url": "https://research.draconitic.com/paper/63x730jfaa6jf",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}