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Some of the synthesized conjugates showed significantly relevant bioactivity against mammalian cells and in animal models of cancers. Selected UA conjugates were tested against bladder and breast cancer cell lines. The conjugates showed moderate to significantly enhanced antiproliferative activities against Triple Negative Breast Cancer (TNBC; MDA\u2010MB 231), which is an aggressive tumor making up about 10\u201315\u2009% of all breast cancers and bladder (T24 and 5637) cancer cell lines. These properties were superior to the parent UA. Among all the synthesized compounds, <jats:bold>18\u2009c<\/jats:bold> and <jats:bold>18\u2009d<\/jats:bold> have exhibited promising antiproliferative and cytotoxic properties against all tested cancer cell lines. However, <jats:bold>18\u2009d<\/jats:bold> has proved to be exceptionally selective for cancer cell lines, showing more cytotoxicity towards them than normal epithelial cells (MCF\u201012A). Compound <jats:bold>18\u2009d<\/jats:bold> has demonstrated cytotoxicity against tumor cells, including those intrinsically resistant to chemotherapy drugs such as 2\u2010difluoro\u2010deoxy cytidine (Gemcitabine). The activity of the UA conjugates on tumor cells was mediated by multiple cytotoxic mechanisms, including drug\u2010induced cytotoxic autophagy and programmed cell death, indicating a novel possibility of combination therapy.<\/jats:p>","DOI":"10.1002\/cbic.202400376","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T07:41:47Z","timestamp":1722238907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ursolic Acid Conjugates: A New Frontier in Anticancer Drug Development"],"prefix":"10.1002","volume":"25","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley M.","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Augusta University  Augusta, GA 30912 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-7192","authenticated-orcid":false,"given":"Kunj","family":"Bihari Gupta","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center Augusta University  Augusta, GA 30912 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shamta S.","family":"Warang","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center Augusta University  Augusta, GA 30912 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5727-2934","authenticated-orcid":false,"given":"Natasha","family":"Venugopal","sequence":"additional","affiliation":[{"name":"Department of Medicine Penn State Health Milton S. 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