{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:28:40Z","timestamp":1792888120341,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004880","name":"Xinjiang Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004880","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cervical cancer remains a serious threat to women\u2019s health, driving the need for effective and low-toxicity therapeutics. This study designed novel pyrrolidine-chalcone derivatives targeting the MDM2-p53 interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A series of compounds were synthesized and evaluated for cytotoxicity against cervical cancer (HeLa, SiHa, C33A) and normal (H8) cells via CCK-8. The lead compound B1 was further analyzed for p53 pathway activation, apoptosis, and ferroptosis markers (ROS, GSH, MDA, Fe\n                      <jats:sup>2+<\/jats:sup>\n                      ) using western blot, flow cytometry, and assay kits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compound B1 showed potent, nanomolar cytotoxicity (IC\n                      <jats:sub>50<\/jats:sub>\n                      = 0.22, 0.24, and 0.95 \u03bcM for HeLa, SiHa, and C33A, respectively) with low toxicity to H8 cells. B1 activated p53 by downregulating MDM2, inducing cell cycle arrest and apoptosis. Simultaneously, it triggered ferroptosis via ROS accumulation, GSH depletion, elevated MDA and Fe\n                      <jats:sup>2+<\/jats:sup>\n                      , and suppression of SLC7A11\/GPX4.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>B1 is a promising dual-mechanism lead compound against cervical cancer, concurrently activating p53 and ferroptosis, warranting further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1715712","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T11:19:01Z","timestamp":1770376741000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel pyrrolidine-chalcone derivative exhibits synergistic anti-cervical cancer activity by dual-targeting MDM2-p53 axis and ferroptosis pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Hainimu","family":"Xiamuxi","sequence":"first","affiliation":[{"name":"The Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology, College of Pharmacy, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XinYi","family":"Deng","sequence":"additional","affiliation":[{"name":"The Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology, College of Pharmacy, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mourboul","family":"Ablise","sequence":"additional","affiliation":[{"name":"The Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology, College of Pharmacy, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Yan","sequence":"additional","affiliation":[{"name":"The Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology, College of Pharmacy, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madina","family":"Imam","sequence":"additional","affiliation":[{"name":"The Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology, College of Pharmacy, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"The Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology, College of Pharmacy, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MingHui","family":"Zu","sequence":"additional","affiliation":[{"name":"The Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology, College of Pharmacy, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wutiekuer","family":"Wumaier","sequence":"additional","affiliation":[{"name":"The Xinjiang Key Laboratory of Natural Medicine Active Components and Drug Release Technology, College of Pharmacy, Xinjiang Medical University","place":["Urumqi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.3390\/biomedicines10081795","article-title":"Sanguinarine induces H2O2-Dependent apoptosis and ferroptosis in human cervical cancer","volume":"10","author":"Alakkal","year":"2022","journal-title":"Biomedicines"},{"key":"B2","doi-asserted-by":"publisher","first-page":"423","DOI":"10.2174\/0118715206274066231220071557","article-title":"Design, synthesis, and in vitro anti-cervical cancer activity of a novel MDM2-p53 inhibitor based on a chalcone scaffold","volume":"24","author":"Alimujiang","year":"2024","journal-title":"Anticancer Agents Med. 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