Semi-Synthesis and Biological Evaluation of 25(R)-26-Acetoxy-3β,5α-Dihydroxycholest-6-One

Previously, we identified a series of steroids (1–6) that showed potent anti-virus activities against respiratory syncytial virus (RSV), with IC50 values ranging from 3.23 to 0.19 µM. In this work, we first semi-synthesized and characterized the single isomer of 5, 25(R)-26-acetoxy-3β,5α-dihydroxych...

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Veröffentlicht in:Marine drugs 2023-03, Vol.21 (3), p.191
Hauptverfasser: Maimaitiming, Mireguli, Lv, Ling, Zhang, Xuetao, Xia, Shuli, Li, Xin, Wang, Pingyuan, Liu, Zhiqing, Wang, Chang-Yun
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Sprache:eng
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Zusammenfassung:Previously, we identified a series of steroids (1–6) that showed potent anti-virus activities against respiratory syncytial virus (RSV), with IC50 values ranging from 3.23 to 0.19 µM. In this work, we first semi-synthesized and characterized the single isomer of 5, 25(R)-26-acetoxy-3β,5α-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 µM, 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 µM without any impression of normal liver cell proliferation at 20 µM. Among them, the target compound (25R)-5 possessed cytotoxicity activities against 5637 (HTB-9) and HepG2 with IC50 values of 4.8 µM and 15.5 µM, 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.
ISSN:1660-3397
1660-3397
DOI:10.3390/md21030191