{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:43:22Z","timestamp":1792691002431,"version":"4.5.0"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seed Funds for Solution-Based Health Care Research in Priority Areas Relevant to Sindh Province","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT) is one of the central enzymes of purine salvage pathway of protozoan parasites, including\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    . 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\n                    <jats:bold>1\u201317<\/jats:bold>\n                    of paroxetine was synthesized\n                    <jats:italic>via<\/jats:italic>\n                    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\n                    <jats:sup>1<\/jats:sup>\n                    H-, and\n                    <jats:sup>13<\/jats:sup>\n                    C-NMR. These compounds were evaluated for their HGXPRT inhibitory activity\n                    <jats:italic>via in vitr<\/jats:italic>\n                    o UV-based spectrophotometric assay. All derivatives\n                    <jats:bold>1<\/jats:bold>\n                    \u2013\n                    <jats:bold>17<\/jats:bold>\n                    showed varying potential to inhibit the enzyme activity with IC\n                    <jats:sub>50<\/jats:sub>\n                    values between 19.0 to 76.9 \u00b5M, with highest activity showed by compound\n                    <jats:bold>13<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200919.0\u2009\u00b1\u20092.09 \u00b5M) within the series, but remained less potent than the standard (9-deazaguanine, IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200912.00\u2009\u00b1\u20091.0 \u00b5M). 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\n                    <jats:italic>via<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0359519","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:22:41Z","timestamp":1792689761000},"page":"e0359519","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Carbothioamide functionalized paroxetine analogues as antiparasitic agents targeting the hypoxanthine-guanine-xanthine phosphoribosyltransferase enzyme: Synthesis, characterization, biochemical, biophysical, and in silico studies"],"prefix":"10.1371","volume":"21","author":[{"given":"Laleen","family":"Hammal","sequence":"first","affiliation":[{"name":"University of Karachi","place":["Karachi, Pakistan"],"department":["Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center of Chemical and Biological Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukhtiyar","family":"Ali","sequence":"additional","affiliation":[{"name":"University of Karachi","place":["Karachi, Pakistan"],"department":["H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveera","family":"Zafar","sequence":"additional","affiliation":[{"name":"University of Karachi","place":["Karachi, Pakistan"],"department":["Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center of Chemical and Biological Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saima Hassan","family":"Mari","sequence":"additional","affiliation":[{"name":"University of Karachi","place":["Karachi, Pakistan"],"department":["H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Zafar","sequence":"additional","affiliation":[{"name":"University of Karachi","place":["Karachi, Pakistan"],"department":["Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center of Chemical and Biological Sciences"]},{"name":"The University of Lahore","place":["Lahore, Pakistan"],"department":["Institute of Molecular Biology and Biochemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atia-tul-","family":"Wahab","sequence":"additional","affiliation":[{"name":"University of Karachi","place":["Karachi, Pakistan"],"department":["Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center of Chemical and Biological Sciences"]},{"name":"The University of Lahore","place":["Lahore, Pakistan"],"department":["Institute of Molecular Biology and Biochemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hina","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"University of Karachi","place":["Karachi, Pakistan"],"department":["H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences"]},{"name":"The University of Lahore","place":["Lahore, Pakistan"],"department":["Institute of Molecular Biology and Biochemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6422-3022","authenticated-orcid":true,"given":"Sumaira","family":"Javaid","sequence":"additional","affiliation":[{"name":"University of Karachi","place":["Karachi, Pakistan"],"department":["Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center of Chemical and Biological Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Iqbal","family":"Choudhary","sequence":"additional","affiliation":[{"name":"University of Karachi","place":["Karachi, Pakistan"],"department":["Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center of Chemical and Biological Sciences"]},{"name":"University of Karachi","place":["Karachi, Pakistan"],"department":["H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences"]},{"name":"The University of Lahore","place":["Lahore, Pakistan"],"department":["Institute of Molecular Biology and Biochemistry"]},{"name":"Ningbo University","place":["Ningbo, Zhejiang, China"],"department":["Institute of Drug Discovery Technology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"pone.0359519.ref001","first-page":"187","article-title":"Purine and pyrimidine pathways as antimalarial targets","volume-title":"Malaria: Recent Advances and New Perspectives","author":"YVT Minnow","year":"2022"},{"issue":"2","key":"pone.0359519.ref002","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.molbiopara.2016.02.006","article-title":"Kinetic mechanism of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase","volume":"204","author":"S 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