{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:48:38Z","timestamp":1792133318128,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In the present study, a series of curcumin analogs (A1\u2013P3) were designed and synthesized for the inhibition of prostate cancer cells by targeting androgen receptor (AR). All synthesized compounds were structurally characterized by\n                    <jats:sup>1<\/jats:sup>\n                    H NMR,\n                    <jats:sup>13<\/jats:sup>\n                    C NMR, and high\u2010resolution mass spectrometry (HRMS). In\u00a0vitro cytotoxicity assays demonstrated that multiple compounds exhibited comparable or improved cytotoxicity against AR\u2010positive 22Rv1 cells as compared to dimethylcurcumin (DMC, ASC\u2010J9). Among these compounds, compounds A2, A3, B1\u2013B3, D1, F1, F3, G1, G3, H1, and P3 possessed higher selectivity toward prostate cancer cells as compared to DMC. Compounds O1\u2013O3, A1\u2013A3, B1\u2013B3, F1, F3, G1, I1, and P3 exhibited lower cytotoxicity against AR\u2010negative PC\u20103 cells than those against 22Rv1 cells. Based on the cytotoxicity results, the structure\u2013activity relationships were analyzed. In the AR protein suppression assay, compounds O1\u2013O3, A1\u2013A3, and I1 exhibited similar inhibitory effects on both full\u2010length AR (AR\u2010FL) and AR splice variant 7 (AR\u2010V7) as compared to DMC, while compound P3 exhibited significantly enhanced AR\u2010FL suppression effect as compared to DMC. In comparison, compounds B2, B3, F1, and F3 exhibited reduced AR\u2010FL and AR\u2010V7 suppression effects as compared to DMC; B1 and G1 exhibited no significant suppression effect on AR\u2010FL and AR\u2010V7, suggesting that these compounds might inhibit prostate cancer cells by multiple mechanisms. Molecular docking simulations further confirmed that compounds O1\u2013O3, A1\u2013A3, I1, and P3 displayed high targeting ability to AR. The probable binding modes of these compounds to AR were also revealed. By modifying the molecular structure of curcumin, this study identified several compounds (A2, A3, P3) with high inhibitory activity and selectivity against castration\u2010resistant prostate cancer cells by targeting AR\u2010FL and AR\u2010V7. These three compounds are promising new candidates for castration\u2010resistant prostate cancer drug discovery.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70418","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:27:42Z","timestamp":1792132062000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis of Curcumin Analogs Targeting Androgen Receptor for the Selective Inhibition of Castration\u2010Resistant Prostate Cancer Cells"],"prefix":"10.1111","volume":"108","author":[{"given":"Manman","family":"Huang","sequence":"first","affiliation":[{"name":"School of Pharmacy Changzhou University  Changzhou P. R. 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