{
  "abstract": "Hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) is one of the central enzymes of purine salvage pathway of protozoan parasites, including Plasmodium. These parasites are purine auxotrophs, and rely on purine salvage pathway for nucleic acid synthesis. Inhibiting the enzymatic activity can effectively reduce the parasite- induced infections, including malaria. In this context, a library of new carbothioamide derivatives 1–17 of paroxetine was synthesized via single-step chemical transformation strategy with a series of substituted phenyl isothiocyanates. All compounds were purified, and their structures were deduced by using spectroscopic techniques, such as mass, FT-IR, UV, and 1H-, and 13C-NMR. These compounds were evaluated for their HGXPRT inhibitory activity via in vitro UV-based spectrophotometric assay. All derivatives 1–17 showed varying potential to inhibit the enzyme activity with IC50 values between 19.0 to 76.9 µM, with highest activity showed by compound 13 (IC50 = 19.0 ± 2.09 µM) within the series, but remained less potent than the standard (9-deazaguanine, IC50 = 12.00 ± 1.0 µM). Biophysical, molecular docking, and molecular simulation studies were carried out further to analyse the enzyme-inhibitor interaction, and stability. These compounds were predicted to occupy the putative allosteric site of enzyme. Furthermore, cytotoxic profile of these compounds were also evaluated via ADMET analysis and MTT assay, and found to be largely non-cytotoxic. The current study has identified potential hits against HGXPRT enzyme that could further be investigated as anti-parasitic drugs.",
  "abstract_shown": true,
  "affiliations": [
    "Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center of Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.",
    "H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.",
    "Institute of Molecular Biology and Biochemistry, The University of Lahore, LahorePakistan.",
    "Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang, China."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Laleen Hammal"
    },
    {
      "affs": [
        1
      ],
      "name": "Mukhtiyar Ali"
    },
    {
      "affs": [
        0
      ],
      "name": "Naveera Zafar"
    },
    {
      "affs": [
        1
      ],
      "name": "Saima Hassan Mari"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Humaira Zafar"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Atia-Tul- Wahab"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Hina Siddiqui"
    },
    {
      "affs": [
        0
      ],
      "name": "Sumaira Javaid",
      "orcid": "0000-0002-6422-3022"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Muhammad Iqbal Choudhary"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/02wcb7237sjfe.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0359519",
  "fulltext_url": "https://europepmc.org/articles/PMC13690214",
  "id": "02wcb7237sjfe",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0359519",
  "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",
      "2739|Malaria Research and Control"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Biochemical simulations"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzyme inhibitors"
    ],
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      "/Biology and life sciences/Biochemistry/Enzymology/Enzymes"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Enzymes"
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    [
      "plos",
      "/Biology and life sciences/Computational biology/Biochemical simulations"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pharmacology/Drug interactions"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Chemical compounds/Organic compounds/Purines"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Computational chemistry/Molecular dynamics"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Organic chemistry/Organic compounds/Purines"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Physical chemistry/Chemical bonding/Hydrogen bonding"
    ],
    [
      "plos",
      "/Research and analysis methods/Bioassays and physiological analysis/Biochemical analysis/Colorimetric assays/MTT assay"
    ],
    [
      "plos",
      "/Research and analysis methods/Bioassays and physiological analysis/Biochemical analysis/Enzyme assays/MTT assay"
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  "openalex": "W7223245807",
  "pdf_url": "https://europepmc.org/articles/PMC13690214?pdf=render",
  "pmcid": "PMC13690214",
  "pmid": "42911912",
  "published": "2026-10-22",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/02wcb7237sjfe.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:23Z",
      "native_id": "10.1371/journal.pone.0359519",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0359519"
    },
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42911912",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42911912"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:enzymology",
      "subfield": "enzymology-metabolism"
    },
    {
      "field": "biology",
      "origin": "plos:computational biology",
      "subfield": "bioinformatics"
    },
    {
      "field": "medicine",
      "origin": "plos:pharmacology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Carbothioamide functionalized paroxetine analogues as antiparasitic agents targeting the hypoxanthine-guanine-xanthine phosphoribosyltransferase enzyme: Synthesis, characterization, biochemical, biophysical, and in silico studies",
  "title_text": "Carbothioamide functionalized paroxetine analogues as antiparasitic agents targeting the hypoxanthine-guanine-xanthine phosphoribosyltransferase enzyme: Synthesis, characterization, biochemical, biophysical, and in silico studies",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/02wcb7237sjfe",
  "venue": "PLOS One",
  "versions": []
}