Glycosides and Glycoconjugates of the Diterpenoid Isosteviol with a 1,2,3-Triazolyl Moiety: Synthesis and Cytotoxicity Evaluation

Several glycoconjugates of the diterpenoid
isosteviol (16-oxo-ent-beyeran-19-oic acid) with
a 1,2,3-triazolyl moiety were
synthesized, and their cytotoxicity was evaluated against some human
cancer and normal cell lines. Most of the synthesized compounds demonstrated
weak inhibitory activities against the M-HeLa and MCF-7 human cancer
cell lines. Three lead compounds, 54, 56 and 57, exhibited high selective cytotoxic activity
against M-HeLa cells (IC50 = 1.7–1.9 μM) that
corresponded to the activity of the anticancer drug doxorubicin (IC50 = 3.0 μM). Moreover, the lead compounds were not cytotoxic
with respect to a Chang liver human normal cell line (IC50 > 100 μM), whereas doxorubicin was cytotoxic to this cell
line (IC50 = 3.0 μM). It was found that cytotoxic
activity of the lead compounds is due to induction of apoptosis proceeding
along the mitochondrial pathway. The present findings suggest that
1,2,3-triazolyl-ring-containing glycoconjugates of isosteviol are
a promising scaffold for the design of novel anticancer agents.