{
  "abstract": "Herein, dasatinib (DASA) and heme oxygenase-1 (HO-1) inhibitor codrugs were designed and synthesized. Derivatization of DASA was performed by preserving the structural features essential for target inhibition and was rationally guided by molecular modelling studies. Two out of three synthesized codrugs showed the ability to inhibit HO-1 activity in a low micromolar range (i.e., 2.12 and 1.00 μM for TC7 and TC8, respectively), while all derivatives retained a significant capability of inhibiting the cSRC tyrosine kinase with sub-micromolar potency (i.e., 0.0023-0.0255 μM). Of note, derivative TC7 exhibited significant in vitro antiproliferative activity against U87MG glioblastoma cells, likely mediated by HO inhibition and accompanied by a ∼1.5-fold increase in intracellular ROS levels compared with the control. Also, assessment of the most promising codrug, TC7, revealed high chemical and enzymatic stability (t 1/2 >24 h). While additional optimization will be required to further improve its drug-like profile, TC7 emerged as the most promising compound evaluated in this study and represents a suitable starting point for future development. Collectively, these results serve as a proof of concept supporting a potential new codrugs strategy combining HO-1 and cSRC inhibition for glioblastoma therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Drug and Health Sciences, University of Catania viale A. Doria 6 95125 Catania Italy s.intagliata@unict.it +39 095 738 4053.",
    "Department of Pharmacy, \"Federico II\" University of Naples 80131 Naples Italy.",
    "Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology Giza 12587 Egypt.",
    "Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University Ismailia 41522 Egypt."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Valeria Pittalà"
    },
    {
      "affs": [
        0
      ],
      "name": "Loredana Salerno",
      "orcid": "0000-0001-6458-3717"
    },
    {
      "affs": [
        0
      ],
      "name": "Valeria Consoli",
      "orcid": "0000-0001-8961-5818"
    },
    {
      "affs": [
        0
      ],
      "name": "Agata Grazia D'Amico",
      "orcid": "0000-0003-4216-417X"
    },
    {
      "affs": [
        0
      ],
      "name": "Valeria Sorrenti",
      "orcid": "0000-0002-5973-1495"
    },
    {
      "affs": [
        0
      ],
      "name": "Luca Vanella",
      "orcid": "0000-0002-6314-6029"
    },
    {
      "affs": [
        0
      ],
      "name": "Giorgia Centamore"
    },
    {
      "affs": [
        0
      ],
      "name": "Chiara Terlati"
    },
    {
      "affs": [
        0
      ],
      "name": "Sara Mocka",
      "orcid": "0009-0005-5060-0965"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Nunziata Modica",
      "orcid": "0000-0002-6350-931X"
    },
    {
      "affs": [
        0
      ],
      "name": "Giuseppe Romeo",
      "orcid": "0000-0003-2160-4164"
    },
    {
      "affs": [
        1
      ],
      "name": "Marica Erminia Schiano",
      "orcid": "0000-0002-4456-3003"
    },
    {
      "affs": [
        1
      ],
      "name": "Federica Sodano",
      "orcid": "0000-0003-2013-4893"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Mohamed A Helal",
      "orcid": "0000-0002-6304-8285"
    },
    {
      "affs": [
        0
      ],
      "name": "Sebastiano Intagliata",
      "orcid": "0000-0002-0201-1745"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0fpzzpkvgb7qa.bib",
  "cited_by": 0,
  "doi": "10.1039/d6md00227g",
  "fulltext_url": "https://europepmc.org/articles/PMC13684878",
  "id": "0fpzzpkvgb7qa",
  "issns": [
    "2632-8682"
  ],
  "landing_url": "https://europepmc.org/article/MED/42910035",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1605|Synthesis and biological activity"
    ]
  ],
  "openalex": "W7220830976",
  "pdf_url": "https://europepmc.org/articles/PMC13684878?pdf=render",
  "pmcid": "PMC13684878",
  "pmid": "42910035",
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0fpzzpkvgb7qa.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42910035",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42910035"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Synthesis and biological activity",
      "subfield": "organic"
    }
  ],
  "title": "Design, synthesis, and in vitro antiproliferative evaluation of dasatinib/HO-1 inhibitor codrugs towards glioblastoma therapy.",
  "title_text": "Design, synthesis, and in vitro antiproliferative evaluation of dasatinib/HO-1 inhibitor codrugs towards glioblastoma therapy.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/0fpzzpkvgb7qa",
  "venue": "RSC medicinal chemistry",
  "versions": []
}