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In this work, we first semi-synthesized and characterized the single isomer of 5, 25(R)-26-acetoxy-3\u03b2,5\u03b1-dihydroxycholest-6-one, named as (25R)-5, in seven steps from a commercially available compound diosgenin (7), with a total yield of 2.8%. Unfortunately, compound (25R)-5 and the intermediates only showed slight inhibitions against RSV replication at the concentration of 10 \u00b5M, but they possessed potent cytotoxicity activities against human bladder cancer 5637 (HTB-9) and hepatic cancer HepG2, with IC50 values ranging from 3.0 to 15.5 \u00b5M without any impression of normal liver cell proliferation at 20 \u00b5M. Among them, the target compound (25R)-5 possessed cytotoxicity activities against 5637 (HTB-9) and HepG2 with IC50 values of 4.8 \u00b5M and 15.5 \u00b5M, respectively. Further studies indicated that compound (25R)-5 inhibited cancer cell proliferation through inducing early and late-stage apoptosis. Collectively, we have semi-synthesized, characterized and biologically evaluated the 25R-isomer of compound 5; the biological results suggested that compound (25R)-5 could be a good lead for further anti-cancer studies, especially for anti-human liver cancer.<\/jats:p>","DOI":"10.3390\/md21030191","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T03:09:37Z","timestamp":1679281777000},"page":"191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Semi-Synthesis and Biological Evaluation of 25(R)-26-Acetoxy-3\u03b2,5\u03b1-Dihydroxycholest-6-One"],"prefix":"10.3390","volume":"21","author":[{"given":"Mireguli","family":"Maimaitiming","sequence":"first","affiliation":[{"name":"Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine 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