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

  • J Nat Prod. 2020 Aug 28;83(8):2367-2380. doi: 10.1021/acs.jnatprod.0c00134.
Olga V Andreeva  1 ,  Bulat F Garifullin  1 ,  Radmila R Sharipova  1 ,  Irina Yu Strobykina  1 ,  Anastasiya S Sapunova  1 ,  Alexandra D Voloshina  1 ,  Mayya G Belenok  1 ,  Alexey B Dobrynin  1 ,  Leysan R Khabibulina  1 ,  Vladimir E Kataev  1
Affiliations
  • 1. Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Street, 8, Kazan, 420088, Russian Federation.
PMID: 32786882 DOI: 10.1021/acs.jnatprod.0c00134
Abstract

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.