Synthesis, antimicrobial and cytotoxic activities, and structure-activity relationships of gypsogenin derivatives against human cancer cells

Article abstract of DOI:10.1016/j.ejmech.2014.05.084

A series of gypsogenin (1) derivatives (1a-i) was synthesized in good yields, and the derivatives' structures were established using UV, IR, ¹H NMR, ¹³C NMR, and LCMS spectroscopic data. Among the tested compounds, 1a, 1b, 1d, 1e, and gypsogenin (1) showed antimicrobial activities against Bacillus subtilis and Bacillus thrungiensis, with inhibition zones of 10-14 mm. In addition, compounds 1b, 1d, and 1e showed antimicrobial activities against Bacillus cereus, with inhibition zones of 9-14 mm. Using six human cancer cell lines in vitro, the cytotoxic activities of all tested compounds were determined by calculating the IC₅₀ values. Doxorubicin and paclitaxel were used as controls. Among the tested compounds, 1a, 1c, and 1d had inhibitory effects with IC₅₀ values of 3.9 μM (HL-60 cells), 5.15 μM (MCF-7 cells), and 5.978 μM (HL-60), respectively. To determine the type of cell death, Hoechst 33258 (HO) and propidium iodide (PI) double staining was used. Especially, gypsogenin (1) and compound 1a triggered the apoptotic mechanism at a concentration of 20 μM. Thus, gypsogenin (1) and compounds 1a, 1c, and 1d possess varying degrees of biological activities and can be considered as potential antitumor agents.