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In the present work, 33 3\u2010substituted BA derivatives comprising 13 previously unreported ones were synthesized. Among them, a syringoyl analog (3\u2010deoxy\u20103\u03b2\u2010syringoylamino\u2010betulinic acid [DSABA]) showed significantly enhanced cytostatic activity against specific tumor cell lines. Further in vitro antitumor evaluation revealed that DSABA induced cell death and G\n                    <jats:sub>0<\/jats:sub>\n                    \/G\n                    <jats:sub>1<\/jats:sub>\n                    phase arrest, as well as inhibited the migration and invasion, of two breast cancer cell lines, and the in vivo antitumor efficacy was subsequently validated in an orthotopic autograft mouse model. Mechanistically, DSABA may exert its antitumor effect by modulating the RAS\/RAF\/MEK\/ERK signaling pathway, as evidenced by a series of in vitro and in vivo experiments. In conclusion, this study has identified DSABA as a promising antitumor candidate, providing a foundation for the future investigation of related structural analogs.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202502436","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T20:13:44Z","timestamp":1764792824000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["3\u2010Deoxy\u20103\u03b2\u2010syringoylamino\u2010betulinic acid Reduces Breast Tumor Growth and Lung Colonization, With Associated Downregulation of the RAS\/RAF\/MEK\/ERK Pathway"],"prefix":"10.1002","volume":"23","author":[{"given":"Hu","family":"Liu","sequence":"first","affiliation":[{"name":"School of Chemistry and Chemical Engineering University of Jinan  Jinan China"},{"name":"School of Biological Science and Technology University of Jinan  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei\u2010Wen","family":"Su","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology University of Jinan  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Song","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology University of Jinan  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology University of Jinan  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peipei","family":"Shan","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5959-6473","authenticated-orcid":false,"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology University of Jinan  Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00679"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(21)60097-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871523018666190426152049"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2020.112608"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104954"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2018.11.018"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.4639"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(21)60097-3"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155858"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26051381"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12010177"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28041725"},{"key":"e_1_2_9_14_1","first-page":"25","article-title":"Betulinic Acid Targets Drug\u2010Resistant Human Gastric Cancer Cells by Inducing Autophagic Cell Death, Suppresses Cell Migration and Invasion, and Modulates the ERK\/MEK Signaling Pathway","volume":"69","author":"Wang H.","year":"2021","journal-title":"Acta Biochimica Polonica"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA07602H"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115472"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2025.118062"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2021.105101"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106741"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(03)00724-8"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112815"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.02.012"},{"key":"e_1_2_9_23_1","first-page":"168","article-title":"Mitochondria, Reactive Oxygen Species and Apoptosis","volume":"28","author":"Zhao Y. 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