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

Abstract

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 <b>7a</b>-<b>7j</b>, for an oxime derivative <b>3</b> and a (2,4-dinitrophenyl)hydrazono derivative <b>4</b>. In particular, the IC₅₀ values of compounds <b>4</b> (IC₅₀ = 2.97 ± 1.13 µΜ) and <b>7 g</b> (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 <b>4</b> and <b>7 g</b> to act mainly by an arrest of the tumour cells in the S phase of the cell cycle. In addition, compounds <b>4</b> and <b>7 g</b> triggered the apoptotic pathway in cancer cells, showing high apoptosis ratios.