Semi-Synthesis and Biological Evaluation of 25( R) -26-Acetoxy-3 β ,5 α -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-3 β ,5 α -dihydroxycholest-6-one, named as (25 R )- 5 , in seven steps from a commercially available compound diosgenin ( 7 ), with a total yield of 2.8%. Unfortunately, compound (25 R )- 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 (25 R )- 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 (25 R )- 5 inhibited cancer cell proliferation through inducing early and late-stage apoptosis. Collectively, we have semi-synthesized, characterized and biologically evaluated the 25 R -isomer of compound 5 ; the biological results suggested that compound (25 R )- 5 could be a good lead for further anti-cancer studies, especially for anti-human liver cancer.