{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T03:28:41Z","timestamp":1783999721887,"version":"3.55.0"},"reference-count":60,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah Bint Abdulrahman University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Innovative paracetamol\u2010alkanesulfonate conjugates (\n                    <jats:bold>5a\u2013l<\/jats:bold>\n                    ) were designed and synthesized through a multi\u2010step process starting with acetaminophen. Their dual functionality as anticancer agents and inhibitors of cyclooxygenase\u20102 (COX\u20102), created through a multi\u2010step reaction sequence beginning with acetaminophen, was investigated. The anticancer activity was assessed across seven different cancer cell lines: HOS (osteosarcoma), A\u2010549 (lung), MCF\u20107 (breast), HT\u201029 (colon), PC3 (prostate), Caco\u20102 (colorectal), and HCT\u2010116 (colorectal). Among these conjugates,\n                    <jats:bold>5d<\/jats:bold>\n                    showed exceptional activity against the Caco\u20102 cell line. The tested compounds demonstrated potent COX\u20102 activity with IC\n                    <jats:sub>50<\/jats:sub>\n                    values extending from 0.052 to 0.096\u2009\u00b5M. Moreover, compounds\n                    <jats:bold>5d<\/jats:bold>\n                    ,\n                    <jats:bold>5h<\/jats:bold>\n                    , and\n                    <jats:bold>5i<\/jats:bold>\n                    displayed remarkable COX\u20102 selectivity, as reflected by their high selectivity indices and substantially weaker COX\u20101 inhibition compared to celecoxib, the reference drug. These results are further supported by COX\u20102 overexpression assays in Caco\u20102 cells, where compound\n                    <jats:bold>5d<\/jats:bold>\n                    significantly downregulated COX\u20102 protein levels, reinforcing its potential as a safer and selective COX\u20102 inhibitor. Further investigation into the mechanism of action revealed that compound\n                    <jats:bold>5d<\/jats:bold>\n                    promotes apoptosis by enhancing the expression of the proapoptotic Bax protein while simultaneously reducing levels of antiapoptotic Bcl\u20102, ultimately leading to increased caspase\u20103 expression, cell cycle arrest, and apoptosis. To understand the structural basis for this activity, molecular docking and dynamics simulations were conducted, which confirmed that compound\n                    <jats:bold>5d<\/jats:bold>\n                    forms stable interactions within the catalytic pockets of both Bcl\u20102 and BAX receptors. These findings suggest that compound\n                    <jats:bold>5d<\/jats:bold>\n                    has significant potential as a dual\u2010acting therapeutic agent.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70125","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T06:26:52Z","timestamp":1760682412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dual Anticancer and COX\u20102 Inhibitory Activity of Tailored Paracetamol\u2010Alkanesulfonate Conjugates: A Promising Therapeutic Approach"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9020-9956","authenticated-orcid":false,"given":"Asmaa F.","family":"Kassem","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Science and Humanities in Al\u2010Kharj Prince Sattam Bin Abdulaziz University Al\u2010Kharj Saudi Arabia"},{"name":"Chemistry of Natural and Microbial Products Department Pharmaceutical and Drug Industries Research Institute, National Research Centre Giza Dokki Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa M.","family":"Mounier","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy Pharmaceutical and Drug Industries Research Institute, National Research Centre Giza Dokki Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0849-380X","authenticated-orcid":false,"given":"Mostafa I.","family":"Abdelglil","sequence":"additional","affiliation":[{"name":"College of Medical Technical Al\u2010Farahidi University Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3445-4065","authenticated-orcid":false,"given":"Sameh","family":"Abdelwahed","sequence":"additional","affiliation":[{"name":"Department of Chemistry Prairie View A&amp;M University Prairie View Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"El\u2010Rashedy","sequence":"additional","affiliation":[{"name":"Chemistry of Natural and Microbial Products Department National Research Centre Giza Dokki Egypt"},{"name":"Department of Organic and Medicinal Chemistry, Faculty of Pharmacy University of Sadat City Sadat City Menoufia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6286-319X","authenticated-orcid":false,"given":"Asmaa","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy Princess Nourah bint Abdulrahman University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9617-4985","authenticated-orcid":false,"given":"Mahmoud G. A.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science Northern Border University Arar Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6692-6952","authenticated-orcid":false,"given":"Aladdin M.","family":"Srour","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Chemistry Pharmaceutical and Drug Industries Research Institute, National Research Centre Giza Dokki Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"C. P.Wild E.Weiderpass andB. 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