{
  "abstract": "Panduratin A (1), a cyclohexenyl chalcone isolated from Boesenbergia rotunda, has been reported to exhibit various biological activities, including antitumor effects. However, its antiproliferative activity against glioblastoma cells and glioblastoma-derived cancer stem-like cells (CSCs), and the molecular basis of this activity, remain incompletely elucidated. In this study, we evaluated the antiproliferative activity of 1 against U-251 MG glioblastoma cells (non-CSCs) and U-251 MG CSCs and found that 1 exhibited potent activity against both cell populations. To investigate the structural features associated with this activity, cyclohexenyl chalcone derivatives of 1 (2–11) were synthesized through a chalcone intermediate generated from an acetophenone precursor, followed by Diels–Alder reactions with dienes. Structure–activity relationship analysis, particularly in U-251 MG non-CSCs, suggested that the phenolic oxygen functionalities of 1 contribute to its potent activity, whereas some acetylated derivatives retained moderate activity. Based on this observation, affinity-based target identification using U-251 MG non-CSC extracts identified prohibitin 2 (PHB2), an inner mitochondrial membrane protein, as a candidate binding protein for 1. In these cells, 1 also markedly altered the mitochondrial morphology and reduced the mitochondrial membrane potential. Together, these findings suggest that the antiproliferative activity of 1 in U-251 MG glioblastoma cells may be associated with PHB2 and mitochondrial alterations.\n\nGraphical Abstract:\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11418-026-02095-6.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Pharmacognosy, Kyoto Pharmaceutical University, 1, Misasagi-Shichono-cho, Yamashina-ku, Kyoto-shi, Kyoto, 607-8412 Japan",
    "Laboratory of Clinical and Translational Physiology, Kyoto Pharmaceutical University, 5, Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto-shi, Kyoto, 607-8414 Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kousuke Araki",
      "orcid": "0009-0000-6166-2452"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuna Yoshitani"
    },
    {
      "affs": [
        0
      ],
      "name": "Rina Okamoto"
    },
    {
      "affs": [
        1
      ],
      "name": "Shigekuni Hosogi"
    },
    {
      "affs": [
        0
      ],
      "name": "Ryota Fujikawa"
    },
    {
      "affs": [
        0
      ],
      "name": "Moe Kaneko"
    },
    {
      "affs": [
        0
      ],
      "name": "Reia Ishikura"
    },
    {
      "affs": [
        0
      ],
      "name": "Chiho Shimadzu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuzuki Takahashi"
    },
    {
      "affs": [
        0
      ],
      "name": "Rina Mantani"
    },
    {
      "affs": [
        0
      ],
      "name": "Tomoe Ohta",
      "orcid": "0000-0002-4698-651X"
    },
    {
      "affs": [
        0
      ],
      "name": "Seikou Nakamura",
      "orcid": "0000-0003-3172-299X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a5jdk5fj2kx8v.bib",
  "cited_by": 0,
  "doi": "10.1007/s11418-026-02095-6",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723570/",
  "id": "a5jdk5fj2kx8v",
  "issns": [
    "1340-3443",
    "1861-0293"
  ],
  "landing_url": "https://doi.org/10.1007/s11418-026-02095-6",
  "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": [
    [
      "heading",
      "Original Paper"
    ],
    [
      "openalex",
      "1312|Bioactive natural compounds"
    ]
  ],
  "openalex": "W7221586242",
  "pdf_url": "https://link.springer.com/content/pdf/10.1007/s11418-026-02095-6.pdf",
  "pmcid": "PMC13723570",
  "pmid": "42870211",
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a5jdk5fj2kx8v.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:11Z",
      "native_id": "PMC13723570",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s11418-026-02095-6"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Bioactive natural compounds",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Antiproliferative activities of panduratin A and its derivatives against U-251 MG glioblastoma cells and U-251 MG cancer stem-like cells: structure–activity relationships and identification of PHB2 as a candidate binding protein",
  "title_text": "Antiproliferative activities of panduratin A and its derivatives against U-251 MG glioblastoma cells and U-251 MG cancer stem-like cells: structure–activity relationships and identification of PHB2 as a candidate binding protein",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:22Z",
  "url": "https://research.draconitic.com/paper/a5jdk5fj2kx8v",
  "venue": "Journal of Natural Medicines",
  "versions": []
}