{
  "abstract": "The α-1,6-fucosyltransferase (FUT8) mediated core fucosylation is responsible for several pathophysiological processes, including prostate cancer progression. FUT8 is a promising therapeutic target owing to its effects on cell migration and its capacity to convert androgen-dependent prostate cancer cells into androgen-independent cells. This study, therefore, investigates potential FUT8 inhibitors as therapeutic options for prostate cancer by targeting FUT8-mediated core fucosylation using in vitro, biophysical, and computational approaches. Eight of the 265 compounds showed significant cytotoxicity against the prostate cancer (PC3) cell line in in vitro screening. These compounds demonstrated dose-dependent reductions in cell viability, with IC50 values ranging from 2.94 ± 0.04 to 75.82 ± 2.10 µM. These compounds were non-cytotoxic against the normal human fibroblast (BJ) cell line. Biophysical and in silico analyses were conducted on active compounds to obtain atomic-level structural details of interactions between FUT8 and ligands. Among these, compounds 1, 3, 6, and 7 showed significant Saturation Transfer Difference Nuclear Magnetic Resonance (STD-NMR) effects and induced a decrease in the melting temperature (Tm) of FUT8 in the differential scanning fluorimetry (DSF) assay (0.25°C–9°C), indicating ligand-associated destabilization of the protein. Molecular docking and molecular dynamics simulation results showed that compounds 1, 2, 3, 4, 6, and 7 stably interacted with the FUT8 binding site. These compounds also exhibited anti-migratory activity in a scratch cell assay, as indicated by scratch closure of only 3.14% to 14.18%, compared with 45.45% to 100% in the control group. Our study identified compounds 1, 3, 6, and 7 as promising leads against the FUT8 enzyme. Further mechanistic and in vivo studies are required to evaluate their mechanisms of action for FUT8-driven prostate cancer progression.",
  "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, Lahore, Pakistan",
    "National Facility for Coastal & Marine Research (NFCMR) & Centre for Ocean Research (COR), Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India",
    "Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Muhammad Awais"
    },
    {
      "affs": [
        1
      ],
      "name": "Noor Rahman"
    },
    {
      "affs": [
        2
      ],
      "name": "Sumaira Javaid"
    },
    {
      "affs": [
        3
      ],
      "name": "Atia-tul- Wahab"
    },
    {
      "affs": [
        4
      ],
      "name": "Thirugnanasambandam Rajendran"
    },
    {
      "name": "M. Iqbal Choudhary"
    },
    {
      "name": "Humaira Zafar"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ca08dfbmhygbg.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0349302",
  "fulltext_url": null,
  "id": "ca08dfbmhygbg",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0349302",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Glycosylation and Glycoproteins Research"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Biochemical simulations"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Protein interactions"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Biochemical simulations"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Genitourinary tract tumors/Prostate cancer"
    ],
    [
      "plos",
      "/Medicine and health sciences/Urology/Prostate diseases/Prostate cancer"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Computational chemistry/Molecular docking"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Computational chemistry/Molecular dynamics"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Physical chemistry/Chemical bonding/Hydrogen bonding"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Thermodynamics/Free energy"
    ],
    [
      "plos",
      "/Research and analysis methods/Chemical characterization/Binding analysis"
    ]
  ],
  "openalex": "W7220391080",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0349302&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/ca08dfbmhygbg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.1371/journal.pone.0349302",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0349302"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:computational biology",
      "subfield": "bioinformatics"
    },
    {
      "field": "chemistry",
      "origin": "plos:computational chemistry",
      "subfield": "theoretical"
    },
    {
      "field": "medicine",
      "origin": "plos:cancers and neoplasms",
      "subfield": "oncology"
    }
  ],
  "title": "Identification of new fucosyltransferase-8 inhibitors: An integrated biochemical, biophysical, and computational approach",
  "title_text": "Identification of new fucosyltransferase-8 inhibitors: An integrated biochemical, biophysical, and computational approach",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/ca08dfbmhygbg",
  "venue": "PLOS One",
  "versions": []
}