Preparations of vitamin D analogs, spirostanols and furostanols from diosgenin and their cytotoxic activities

Vitamin D analogs 12 and 13 having a spiro ring in the side chain, various spirostanols 18-21, 26, 27, 29 and 37, and furostanols 34-36 having SCN and SeCN groups at the 26 position were prepared from diosgenin 1 via (20S,22R,25R)-spirost-1α,2α-epoxy-4,6-dien-3-one 19 as a key intermediate. The cytotoxic activities of these derivatives as well as 1 on scarcely P-gp-expressed HCT 116 cells and P-gp-overexpressed Hep G2 cells were examined by MTT assay. Furostanols 34 (IC50 value: 4.9 ± 0.3 μM) and 36 (IC50 value: 1.3 ± 0.2 μM) exhibited marked cytotoxic effects on HCT 116 cells, and spirostanol 29 (IC50 value: 2.4 ± 0.8 μM) and furostanol 36 (IC50 value: 2.8 ± 0.4 μM) on Hep G2 cells. Furthermore, the effects of vitamin D analog 12, spirostanol 26 and furostanol 36 on apoptosis-signaling pathways were investigated. Compounds 12 and 26 overexpressed p53 and Bax mRNAs, while compound 36 overexpressed only Bax mRNA.