Structure–function relationship for saponin effects on cell cycle arrest and apoptosis in the human 1547 osteosarcoma cells: a molecular modelling approach of natural molecules structurally close to diosgenin

In this paper, eight natural molecules structurally close to diosgenin (five saponins: diosgenin, hecogenin, tigogenin, sarsasapogenin, smilagenin; two steroidal alkaloids: solasodine, solanidine; one sterol: stigmasterol) have been tested for their biological activities on human 1547 osteosarcoma cells. Differences in activity were studied in term of proliferation rate, cell cycle distribution and apoptosis induction. By using molecular modelling, two structural characteristics were calculated: spatial conformation and electron transfer capacity. The second property has been investigated by the HOMO repartition and the corresponding energy. Correlation between the experimental and the theoretical data permit us to highlight the importance of the hetero-sugar moiety and the 5,6-double bond in the biological activity (apoptosis and cell cycle arrest) on the human 1547 cell line. The importance of conformation at C-5 and C-25 carbon atoms was also discussed.