{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T11:05:23Z","timestamp":1779447923025,"version":"3.53.1"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Ursolic acid (UA) is a natural pentacyclic triterpenoid with notable antitumor activity, yet its poor water solubility and insufficient targeting restrict clinical translation. Methods: Forty novel ursolic acid-phosphine derivatives bearing seven distinct lipophilic cationic moieties were synthesized via C28 modification and structurally characterized by 1H NMR and 13C NMR. Their antitumor activities in PC3-M cells were evaluated via in vitro assays. Mechanistic investigations were performed using transcriptomic analysis and Western blot. Molecular docking was performed to predict the binding profile of Compound 25 with FGFR1. In vivo antitumor efficacy and biosafety were assessed in RM-1 xenograft models in C57BL\/6 mice. Results: Compound 25 (bearing a tris(3,5-dimethylphenyl)phosphine group at the C28 position with an alkyl chain length of five methylene units) exhibited the most potent activity against PC3-M cells, dose-dependently inhibiting proliferation, migration, and invasion and inducing apoptosis. It triggered mitochondrial apoptosis via ROS accumulation and disrupted cytoskeletal homeostasis by suppressing the FGFR1\/KRAS\/RAC1\/PIP4K2 axis. Molecular docking results suggested its strong binding affinity and specificity. In vivo studies confirmed its significant antitumor effect and favorable safety. Conclusions: These results highlight the potential of Compound 25 as a promising lead compound and provide valuable insights for further medicinal chemistry optimization and the development of novel anticancer drugs derived from ursolic acid.<\/jats:p>","DOI":"10.3390\/ph19050726","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:06:21Z","timestamp":1777860381000},"page":"726","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological Mechanisms of Ursolic Acid Derivative Against Prostate Cancer via Regulating Cytoskeletal Homeostasis and Apoptotic Pathways"],"prefix":"10.3390","volume":"19","author":[{"given":"Huiyue","family":"Shen","sequence":"first","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolan","family":"Ni","sequence":"additional","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Liu","sequence":"additional","affiliation":[{"name":"People\u2019s Hospital of Ningxia Hui Autonomous, Ningxia Medical University, Yinchuan 750002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"He","sequence":"additional","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0704-7410","authenticated-orcid":false,"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China"},{"name":"International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Teng","sequence":"additional","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China"},{"name":"International Joint Laboratory for Development of Animal and Plant Resources for Food and Medicine, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. 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