{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:58:07Z","timestamp":1791223087131,"version":"4.1.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The\n                    <jats:italic>\u03b1<\/jats:italic>\n                    -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\n                    <jats:italic>in vitro<\/jats:italic>\n                    , biophysical, and computational approaches. Eight of the 265 compounds showed significant cytotoxicity against the prostate cancer (PC3) cell line in\n                    <jats:italic>in vitro<\/jats:italic>\n                    screening. These compounds demonstrated dose-dependent reductions in cell viability, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 2.94\u2009\u00b1\u20090.04 to 75.82\u2009\u00b1\u20092.10 \u00b5M. These compounds were non-cytotoxic against the normal human fibroblast (BJ) cell line. Biophysical and\n                    <jats:italic>in silico<\/jats:italic>\n                    analyses were conducted on active compounds to obtain atomic-level structural details of interactions between FUT8 and ligands. Among these, compounds\n                    <jats:bold>1<\/jats:bold>\n                    ,\n                    <jats:bold>3<\/jats:bold>\n                    ,\n                    <jats:bold>6<\/jats:bold>\n                    , and\n                    <jats:bold>7<\/jats:bold>\n                    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\u00b0C\u20139\u00b0C), indicating ligand-associated destabilization of the protein. Molecular docking and molecular dynamics simulation results showed that compounds\n                    <jats:bold>1<\/jats:bold>\n                    ,\n                    <jats:bold>2<\/jats:bold>\n                    ,\n                    <jats:bold>3<\/jats:bold>\n                    ,\n                    <jats:bold>4<\/jats:bold>\n                    ,\n                    <jats:bold>6<\/jats:bold>\n                    , and\n                    <jats:bold>7<\/jats:bold>\n                    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\n                    <jats:bold>1<\/jats:bold>\n                    ,\n                    <jats:bold>3<\/jats:bold>\n                    ,\n                    <jats:bold>6<\/jats:bold>\n                    , and\n                    <jats:bold>7<\/jats:bold>\n                    as promising leads against the FUT8 enzyme. Further mechanistic and\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies are required to evaluate their mechanisms of action for FUT8-driven prostate cancer progression.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0349302","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:40:41Z","timestamp":1791222041000},"page":"e0349302","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of new fucosyltransferase-8 inhibitors: An integrated biochemical, biophysical, and computational approach"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5090-4919","authenticated-orcid":true,"given":"Muhammad","family":"Awais","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaira","family":"Javaid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atia-tul-","family":"Wahab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thirugnanasambandam","family":"Rajendran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Iqbal","family":"Choudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2104-3862","authenticated-orcid":true,"given":"Humaira","family":"Zafar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"issue":"49","key":"pone.0349302.ref001","doi-asserted-by":"crossref","first-page":"5501","DOI":"10.1038\/onc.2013.206","article-title":"Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches","volume":"32","author":"T Karantanos","year":"2013","journal-title":"Oncogene"},{"issue":"8","key":"pone.0349302.ref002","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.4049\/jimmunol.1200501","article-title":"Impact of immune complex size and glycosylation on IgG binding to human 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Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing; 2006. 84 p."},{"issue":"7","key":"pone.0349302.ref039","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1021\/acs.jctc.1c00302","article-title":"OPLS4: improving force field accuracy on challenging regimes of chemical space","volume":"17","author":"C Lu","year":"2021","journal-title":"J Chem Theory Comput"},{"issue":"2","key":"pone.0349302.ref040","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nprot.2007.30","article-title":"In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro","volume":"2","author":"C-C Liang","year":"2007","journal-title":"Nat Protoc"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349302","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:40:49Z","timestamp":1791222049000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349302"}},"subtitle":[],"editor":[{"given":"Saba","family":"Farooq","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":40,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0349302","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]}}}