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 IC 50 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 IC 50 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 IC 50 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.