{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T20:05:27Z","timestamp":1776542727472,"version":"3.51.2"},"reference-count":23,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2025,11,28]]},"abstract":"<jats:p>\n                    In this study, seven novel dihydroartemisinin\u2013loxoprofen hybrids are designed and synthesized, which exhibits significantly enhanced anticancer activity compared to their parent compounds. Through antiproliferation assays, compound\n                    <jats:bold>5<\/jats:bold>\n                    is identified as the most potent agent, showing remarkable efficacy against acute myeloid leukemia (AML) cell lines, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.013\u2009\u03bcM for HL\u201060 cell, 0.048\u2009\u03bcM for U937 cell, and 0.010\u2009\u03bcM for THP\u20101 cell. The antitumor activity of compound\n                    <jats:bold>5<\/jats:bold>\n                    is more than tenfold higher than that of the parent compounds. Furthermore, fluorescence microscopy and flow cytometry analyses reveal that compound\n                    <jats:bold>5<\/jats:bold>\n                    induces apoptosis in HL\u201060 cells more effectively than the positive drug cytarabine. X\u2010ray single\u2010crystal diffraction analysis confirms the absolute configuration of these compounds. Molecular docking studies demonstrate strong binding affinities between all seven hybrid molecules and COX\u20102 (PDB ID: 5IKR) via hydrophobic interactions, hydrogen bonds, and\n                    <jats:italic>\u03c0<\/jats:italic>\n                    <jats:italic>\u2013\u03c0<\/jats:italic>\n                    stacking with key residues. Evaluations in human normal liver THLE\u20102 cells show favorable selectivity indices (SI\u2009&gt;\u200910), and in silico absorption, distribution, metabolism, and excretion (ADME) predictions indicate high gastrointestinal absorption, CYP3A4\u2010mediated metabolism, and bioavailability of 8.15\u20139.36%. The results highlight the potential of dihydroartemisinin\u2013loxoprofen hybrids as a promising research direction for AML treatment strategies.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500300","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T18:15:01Z","timestamp":1762884901000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design, Synthesis, and Antihematological Tumor Activity of Dihydroartemisinin\u2013Loxoprofen Hybrids"],"prefix":"10.1002","volume":"20","author":[{"given":"Dongsheng","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai 201203 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanna","family":"Pan","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Center for TCM 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