Synthesis And Antitumor Activities Of The Diosgenin Derivatives

Diosgenin is a C27 spiroketal steroidal sapogenin, which shows a wide variety of bioactivities. Diosgenin plays an important role in the synthesis of steroid hormone drugs in the field of traditional pharmaceutical industry. Recently, it has been reported that diosgenin could induce inhibitory action and apoptosis in a wide variety of cancer cell lines. Mechanistically, diosgenin was shown to activate the gene of p53 gene, which can release apoptosis-inducing factor to modulate caspase-3 activity and can inhibit the ERK, JNK, phosphoinositide 3-kinase signal pathways as well as NF-KB. Moreover, diosgenin is an important natural glycosides, which distributes in Dioscorea plant widely. The carbohydrate subunits attached covalently to the backbone of spirostane saponins and diosgenin plays an important role for its good bioactivities. During the previous research of our group,(25S)-5β-spirostane-3β-ol-3-O-β-D-glucopyranosyl(1→2)-β-D-glucopyranoside had been isolated from medicinal plant Disporopsis pernyi Diels and the results of their anti-cancer activity showed good certain inhibitory activities. A serise of diosgenin derivatives were synthesized using diosgenin as raw material.In this project, three synthesis strategies were explored: the first strategy is to conjugate of oligosaccharide and alcoholic hydroxyl of diosgenin derivatives by the direct glycosylation; the second strategy is to connect oligosaccharide with azido and diosgenin derivatives with propargyl via “click” by the indirect glycosylation; the third strategy is to modify the ring of “A” and “B” of diosgenin. In this project, twenty-one diosgenin derivatives were synthesized and their structures were confirmed by 1H NMR, 13 C NMR, 1H-1H COSY and ESI-MS et al.In this project, the anti-cancer activities of diosgenin derivatives were evaluated in human liver cells PLC/PRF/5, human prostate cells PC3, human heukemia cells K562 and HEL, human breast cells MDA-MB231. The screening results showed that compound 56(IC50 = 98.4 μg·mL-1) and compound 59(IC50 = 83.2 μg·mL-1) had inhibitory effect on tumor cell lines PLC/PRF/5. In the other hand, compound 75 exhibited the anti-cancer activities with IC50 values of 23.1, 20.4, 19.8, 25.3 μM for the other four cells, respectively. The results can provide reference for further research of diosgenin derivatives.