{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:39:34Z","timestamp":1790127574126,"version":"4.0.1"},"reference-count":45,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"J. Harold Harrison Endowment Fund","award":["MCDGF4001"],"award-info":[{"award-number":["MCDGF4001"]}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["HT94252310761"],"award-info":[{"award-number":["HT94252310761"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Georgia Cancer Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, exhibits potent anticancer properties; however, its poor solubility and bioavailability limit its therapeutic application. To overcome these challenges and facilitate molecular target identification, a set of biotin-conjugated UA derivatives (5a\u2013d) was synthesized through selective C-28 alkylation and biotinylation. The use of microwave-assisted synthesis significantly enhanced both reaction efficiency and product purity. Among the derivatives, compound 5c exhibited increased cytotoxicity and selectivity against bladder cancer cell lines, surpassing UA in its ability to induce apoptosis, generate reactive oxygen species (ROS), and halt cell cycle progression at the G1 phase. Proteomic profiling revealed that 5c interacts with proteins involved in ER stress, RNA processing, cytoskeletal remodeling, and metabolic regulation. These findings underscore the potential of biotinylated UA derivatives as multifunctional chemical probes for mechanistic studies in the development of targeted therapies for cancer.<\/jats:p>","DOI":"10.3390\/molecules30234588","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T16:47:37Z","timestamp":1764780457000},"page":"4588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Biotin-Linked Ursolic Acid Conjugates as Selective Anticancer Agents and Target-Identification Tools for Cancer Therapy"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5326-7364","authenticated-orcid":false,"given":"Riham M.","family":"Bokhtia","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-7192","authenticated-orcid":false,"given":"Kunj Bihari","family":"Gupta","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabella","family":"Natalini","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2809-5610","authenticated-orcid":false,"given":"Theerth Vikas","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihal","family":"Amineni","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7613-7917","authenticated-orcid":false,"given":"Sophia","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev","family":"Shakuja","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Delhi, New Delhi, Delhi 110007, India"},{"name":"Department of Chemistry, Birla Institute of Technology and Science, Pilani, Rajasthan 333031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3317-9911","authenticated-orcid":false,"given":"Guido F.","family":"Verbeck","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1763-4718","authenticated-orcid":false,"given":"Bal L.","family":"Lokeshwar","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siva S.","family":"Panda","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101900","DOI":"10.1016\/j.toxrep.2025.101900","article-title":"Recent Developments on Ursolic Acid and Its Potential Biological Applications","volume":"14","author":"Arulnangai","year":"2025","journal-title":"Toxicol. 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