{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:07:15Z","timestamp":1788876435854,"version":"build-2803163510"},"reference-count":35,"publisher":"American Chemical Society (ACS)","issue":"35","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018925","name":"Health Commission of Henan Province","doi-asserted-by":"publisher","award":["LHGJ 20220271"],"award-info":[{"award-number":["LHGJ 20220271"]}],"id":[{"id":"10.13039\/100018925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011447","name":"Science and Technology Department of Henan Province","doi-asserted-by":"publisher","award":["262102521015"],"award-info":[{"award-number":["262102521015"]}],"id":[{"id":"10.13039\/501100011447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Henan Academy of Sciences","doi-asserted-by":"publisher","award":["20250602002"],"award-info":[{"award-number":["20250602002"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Henan Academy of Sciences","doi-asserted-by":"publisher","award":["20252202001"],"award-info":[{"award-number":["20252202001"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Henan Academy of Sciences","doi-asserted-by":"publisher","award":["24330222"],"award-info":[{"award-number":["24330222"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Health Commission Key Laboratory of Birth Defect Prevention","doi-asserted-by":"publisher","award":["JBKY2022002"],"award-info":[{"award-number":["JBKY2022002"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Health Commission Key Laboratory of Birth Defect Prevention","doi-asserted-by":"publisher","award":["JBKY2023003"],"award-info":[{"award-number":["JBKY2023003"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Health Commission Key Laboratory of Birth Defect Prevention","doi-asserted-by":"publisher","award":["JBKY2023004"],"award-info":[{"award-number":["JBKY2023004"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Health Commission Key Laboratory of Birth Defect Prevention","doi-asserted-by":"publisher","award":["JBKY2023011"],"award-info":[{"award-number":["JBKY2023011"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Health Commission Key Laboratory of Birth Defect Prevention","doi-asserted-by":"publisher","award":["JBKY2023017"],"award-info":[{"award-number":["JBKY2023017"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In this study, we isolated and structurally characterized a diastereoisomer (1-\u00a0R) of the betulonic acid\u2013zidovudine (AZT) conjugates 1-\u00a0S, a previously reported anticancer lead. The absolute configuration at the C-2 position was determined via 1D\/2D nuclear magnetic resonance (NMR) and optical rotatory dispersion (ORD). Both diastereomers exhibited potent anticancer activity against a panel of human cancer cell lines, with particular efficacy against SMMC-7721 (hepatoma) and A549 (lung carcinoma) cells (IC50 = 3.38\u20134.09 \u03bcM). Mechanistic investigations revealed that 1-\u00a0R induces cell death primarily through a caspase-dependent apoptotic pathway. Notably, the necroptosis inhibitor necrostatin-1 (Nec-1, an inhibitor of necroptosis) provided substantial protection, suggesting that necroptosis may play a more prominent role in 1-\u00a0R compared to that of 1-\u00a0S, although this requires direct comparative validation in future studies. The autophagy inhibitor 3-methyladenine (3-MA, an autophagy inhibitor) partially attenuated cell death, indicating a modulatory role for autophagy. These findings highlight 1-\u00a0R as a promising anticancer agent. Despite its initial isolation as a low-yield byproduct (3.2%), the comparable activity of 1-\u00a0R to 1-\u00a0S, coupled with the conformational plasticity of the C-2 linker, simplifies synthetic requirements and supports its further optimization.<\/jats:p>","DOI":"10.1021\/acsomega.6c05494","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:15:05Z","timestamp":1788297305000},"page":"53072-53081","source":"Crossref","is-referenced-by-count":0,"title":["Separation, Structural\nElucidation, and Anticancer\nActivity of a Diastereoisomer of Betulonic Acid\u2013Zidovudine\nConjugates"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3514-9441","authenticated-orcid":true,"given":"Jinxing","family":"Zhai","sequence":"first","affiliation":[{"name":"Zhengzhou University , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Huanghe Science and Technology College , , ,","place":["Zhengzhou, China, 450063"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Liu","sequence":"additional","affiliation":[{"name":"Huanghe Science and Technology College , , ,","place":["Zhengzhou, China, 450063"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Academy of Sciences , , ,","place":["Zhengzhou, China, 450002"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Tang","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hoon","family":"Park","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoke","family":"Qi","sequence":"additional","affiliation":[{"name":"Henan Academy of Innovations in Medical Science , , ,","place":["Zhengzhou, China, 450000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaonan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Henan Academy of Innovations in Medical Science , , ,","place":["Zhengzhou, China, 450000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Academy of Innovations in Medical Science , , ,","place":["Zhengzhou, China, 450000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaozhen","family":"Kang","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , ,","place":["Zhengzhou, China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Kee","family":"Shin","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]},{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-5674","authenticated-orcid":true,"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , ,","place":["Zhengzhou, China, 450001"]},{"name":"Huanghe Science and Technology College , , ,","place":["Zhengzhou, China, 450063"]},{"name":"Henan Academy of Sciences , , ,","place":["Zhengzhou, China, 450002"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"2026090809110541200_cit1","doi-asserted-by":"publisher","DOI":"10.1351\/goldbook.S05983","volume-title":"\u2018Stereoisomerism\u2019\nin IUPAC Compendium of Chemical Terminology","year":"2025","edition":"5"},{"issue":"11","key":"2026090809110541200_cit2","doi-asserted-by":"publisher","first-page":"4466","DOI":"10.1039\/c000408c","article-title":"Pharmacologically\nactive compounds in the environment and their chirality","volume":"39","author":"Kasprzyl-Hordern","year":"2010","journal-title":"Chem. 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