{
  "abstract": "This study presents the synthesis and biological evaluation of substituted 2-(2,4-dioxothiazolidin-3-yl)-N-phenylacetamides and their thioxo analogues as potential multitarget agents for neurodegenerative diseases. A diverse library of amides was designed to explore structure-activity relationships and synthesized using two complementary approaches: a carbodiimide-mediated coupling and a microwave-assisted procedure. The compounds were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition and antioxidant activity. Several derivatives displayed micromolar dual inhibition, with 2-(4-oxo-2-thioxothiazolidin-3-yl)-N-(3,4,5-trichlorophenyl)acetamide (compound 1h) emerging as the most effective BChE inhibitor (IC₅₀ = 2.91 μM), which is also one of the most potent AChE inhibitors in this series. It acts as a specific, reversible, and competitive inhibitor of both BChE and AChE. Polyhalogenated analogues consistently outperformed their mono- and di-substituted counterparts, highlighting the critical role of lipophilic electron-withdrawing substituents. Within this series, rhodanines were generally preferred over thiazolidine-2,4-diones. Our results have demonstrated that rational modifications of the rhodanine and thiazolidine-2,4-dione cores support further investigation of selected derivatives as multitarget cholinesterase inhibitors with complementary antioxidant properties.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University Akademika Heyrovského 1203 500 03 Hradec Králové Czech Republic martin.kratky@faf.cuni.cz.",
    "Institute of Environmental and Chemical Engineering, Faculty of Chemical Technology, University of Pardubice Studentská 573 532 10 Pardubice Czech Republic.",
    "Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice Studentská 573 532 10 Pardubice Czech Republic sarka.stepankova@upce.cz."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Enikő Šikorová",
      "orcid": "0000-0002-9146-573X"
    },
    {
      "affs": [
        0
      ],
      "name": "Adéla Kyslíková"
    },
    {
      "affs": [
        0
      ],
      "name": "Markéta Švarcová"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiří Palarčík",
      "orcid": "0000-0003-3763-4341"
    },
    {
      "affs": [
        2
      ],
      "name": "Šárka Štěpánková",
      "orcid": "0000-0002-1969-5258"
    },
    {
      "affs": [
        0
      ],
      "name": "Martin Krátký",
      "orcid": "0000-0002-4600-8409"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ecgd934zc9mcb.bib",
  "cited_by": 0,
  "doi": "10.1039/d6md00502k",
  "fulltext_url": "https://europepmc.org/articles/PMC13635992",
  "id": "ecgd934zc9mcb",
  "issns": [
    "2632-8682"
  ],
  "landing_url": "https://europepmc.org/article/MED/42835501",
  "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",
      "2736|Cholinesterase and Neurodegenerative Diseases"
    ]
  ],
  "openalex": "W7203665833",
  "pdf_url": "https://europepmc.org/articles/PMC13635992?pdf=render",
  "pmcid": "PMC13635992",
  "pmid": "42835501",
  "published": "2026-08-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ecgd934zc9mcb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42835501",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42835501"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Cholinesterase and Neurodegenerative Diseases",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Rhodanine and 2,4-dioxothiazolidine-based amides: synthesis and evaluation as dual-action cholinesterase inhibitors and antioxidants.",
  "title_text": "Rhodanine and 2,4-dioxothiazolidine-based amides: synthesis and evaluation as dual-action cholinesterase inhibitors and antioxidants.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/ecgd934zc9mcb",
  "venue": "RSC medicinal chemistry",
  "versions": []
}