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

• Published in: Journal of natural products (Washington, D.C.) Vol. 83; no. 8; pp. 2367 - 2380
• Main Authors: Andreeva, Olga V, Garifullin, Bulat F, Sharipova, Radmila R, Strobykina, Irina Yu, Sapunova, Anastasiya S, Voloshina, Alexandra D, Belenok, Mayya G, Dobrynin, Alexey B, Khabibulina, Leysan R, Kataev, Vladimir E
• Format: Journal Article
• Language: English
• Published: American Chemical Society and American Society of Pharmacognosy 28-08-2020
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.0c00134

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.