Synthesis of gypsogenin derivatives with capabilities to arrest cell cycle and induce apoptosis in human cancer cells

Thirty-two gypsogenin derivatives were synthesized and screened for their cytotoxic activities. Their structures were established using IR, ¹H NMR, ¹³C NMR, and LC-MS spectroscopic data. In MTT assays nearly all the compounds displayed good cytotoxicity in the low μM range for several human tumour cell lines (A549, LOVO, SKOV3 and HepG2). Low IC₅₀ values were obtained especially for the carboxamides 7a-7j, for an oxime derivative 3 and a (2,4-dinitrophenyl)hydrazono derivative 4. In particular, the IC₅₀ values of compounds 4 (IC₅₀ = 2.97 ± 1.13 µΜ) and 7 g (IC₅₀ = 3.59 ± 2.04 µΜ) against LOVO cells were found to be much lower than those of the Other derivatives and parent compound. These compounds were submitted to an extensive biological testing and proved compounds 4 and 7 g to act mainly by an arrest of the tumour cells in the S phase of the cell cycle. In addition, compounds 4 and 7 g triggered the apoptotic pathway in Cancer cells, showing high Apoptosis ratios.

apoptosis; cell cycle arrest; cytotoxic activity; gypsogenin derivatives.