{
  "abstract": "To develop human carbonic anhydrase (hCA) IX/XII-targeted therapeutics for glioblastoma multiforme (GBM), novel dithiocarbamate (DTC)-based compounds were synthesized and evaluated for their inhibitory activity against hCA I, II, IX, and XII isoforms. The most potent hCA IX/XII inhibitors were further investigated for their cytotoxic activity against U87 and T98 glioblastoma cells, selectivity toward healthy neuronal cells, and their effects on oxidative stress, inflammatory mediators, and cell death-related pathways. Compounds 4, 9, and 30 emerged as the most promising candidates, with compounds 9 and 30 exhibiting potent cytotoxic activity against both U87 and T98 cells. These compounds acted as dual hCA IX/XII inhibitors with a clear preference for hCA XII. Compounds 9 and 30 modulated the oxidative stress–inflammation axis through regulation of cellular redox balance, and inflammation-associated mediator profiles, including IL-1β, IL-10, TNF-α, and TGF-β. Compound 4 also attenuated oxidative stress and inflammatory signaling in U87 cells. Molecular docking studies supported the experimental findings by revealing favorable binding interactions within the active sites of hCA IX and XII, providing a structural basis for their inhibitory activities. Collectively, these findings identify compounds 4, 9, and 30 as promising DTC-based compounds for GBM therapy through the combined modulation of tumor-associated CAs, oxidative stress, inflammatory, and cell death-related pathways.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Türkiye",
    "Department of Food Technology, Vocational College of Technical Science, Ataturk University, 25240 Erzurum, Türkiye",
    "Department of Nanoscience and Nanoengineering, Institute of Natural and Applied Sciences, Ataturk University, 25240 Erzurum, Türkiye",
    "Department of Pharmacology, Faculty of Dentistry, Atatürk University, 25240 Erzurum, Türkiye",
    "Vocational School of Health Services, Department of Pharmacy Services, Ataturk University, 25240 Erzurum, Türkiye",
    "Department of Pharmaceutical Chemistry, Graduate School, Anadolu University, 26470 Eskişehir, Türkiye",
    "Department of Medical Pharmacology, Faculty of Medicine, Ataturk University, 25240 Erzurum, Türkiye",
    "Department of Nursing, Faculty of Health Sciences, Sakarya University of Applied Sciences, 54187 Sakarya, Türkiye",
    "Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Selçuk University, 42130 Konya, Türkiye"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mehlika Dilek Altıntop",
      "orcid": "0000-0002-8159-663X"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Hayrunnisa Nadaroglu",
      "orcid": "0000-0002-0536-4212"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Fatma Yesilyurt"
    },
    {
      "affs": [
        5
      ],
      "name": "Nalan Yılmaz Savaş"
    },
    {
      "affs": [
        6
      ],
      "name": "Ruken Avsaroglu"
    },
    {
      "affs": [
        7
      ],
      "name": "Azize Alaylı",
      "orcid": "0000-0002-7568-6970"
    },
    {
      "affs": [
        8
      ],
      "name": "Kaan Küçükoğlu",
      "orcid": "0000-0001-8977-9775"
    },
    {
      "affs": [
        6
      ],
      "name": "Ahmet Hacimuftuoglu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ahmet Özdemir",
      "orcid": "0000-0003-0280-5550"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8mg3a29ma9bhd.bib",
  "cited_by": 0,
  "doi": "10.3390/molecules31203593",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707839/?tool=EBI",
  "id": "8mg3a29ma9bhd",
  "issns": [
    "1420-3049"
  ],
  "landing_url": "https://www.mdpi.com/1420-3049/31/20/3593",
  "language": "eng",
  "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",
      "1312|Enzyme function and inhibition"
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  "openalex": "W7221077432",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707839/pdf/?tool=EBI",
  "pmcid": "PMC13707839",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/8mg3a29ma9bhd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:42Z",
      "native_id": "10.3390/molecules31203593",
      "source": "crossref",
      "url": "https://www.mdpi.com/1420-3049/31/20/3593"
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    {
      "first_seen": "2026-10-30T12:21:44Z",
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Enzyme function and inhibition",
      "subfield": "molecular-biology"
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  ],
  "title": "Design, Synthesis, and Biological Evaluation of Novel Dithiocarbamate-Based Human Carbonic Anhydrase IX/XII Inhibitors as Potential Anti-Glioblastoma Agents",
  "title_text": "Design, Synthesis, and Biological Evaluation of Novel Dithiocarbamate-Based Human Carbonic Anhydrase IX/XII Inhibitors as Potential Anti-Glioblastoma Agents",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:44Z",
  "url": "https://research.draconitic.com/paper/8mg3a29ma9bhd",
  "venue": "Molecules",
  "versions": []
}