Synthesis and biological evaluation of the glycoside (25R)-3ß,16ß-diacetoxy-22-oxocholest-5-en-26-yl ß-d-glucopyranoside: a selective anticancer agent in cervicouterine cell lines.

The synthesis and biological evaluation of the new cholestane glycoside (25R)-3ß,16ß-diacetoxy-22-oxocholest-5-en-26-yl ß-d-glucopyranoside starting from diosgenin is described. This compound showed selective antiproliferative activity against CaSki, ViBo, and HeLa cervicouterine cancer cells. Its effect on the cell-cycle was determined. The cytotoxic effects of the title compound on cervicouterine cancer cell lines and human lymphocytes indicate that the main cell death process is not necrosis; hence it is not cytotoxic. The title compound induced apoptosis in cervicouterine cancer cells. Importantly, the antiproliferative activity on tumor cells did not affect the proliferative potential of peripheral blood lymphocytes. The title compound showed selective antitumor activity and greater antiproliferative activity than its aglycon, and therefore serves as a promising lead candidate for further optimization.

Synthesis of 26-hydroxy-22-oxocholestanic frameworks from diosgenin and hecogenin and their in vitro antiproliferative and apoptotic activity on human cervical cancer CaSki cells.

Certain steroidal compounds have demonstrated an antiproliferative effect against several tumor cell lines; however, their complete role on cancer cells is not currently established. Herein, we report the synthesis and evaluation of two new 26-hydroxy-22-oxocholestanic steroids on cervical cancer CaSki cells. The title compounds were prepared from diosgenin and hecogenin in excellent yields. We determined their effect on cell proliferation, cell cycle, and cell death. The cytotoxic effect of the title compounds on CaSki and human lymphocytes was also evaluated, indicating that the main cell death process is not necrosis; the null effect on lymphocytes implies that they are not cytotoxic. The observation of apoptotic bodies as well as the increase in the expression of active caspase-3 along with the fragmentation of DNA confirmed that such new cholestanic frameworks induced apoptosis in tumor cells. Significantly, their antiproliferative activity on tumor cells did not affect the proliferative potential of normal fibroblasts from cervix and peripheral blood lymphocytes. The title compounds show selective antitumor activity and therefore serve as promising lead candidates for further optimization.