Synthesis and anti-cancer activities of glycosides and glycoconjugates of diterpenoid isosteviol

• Published in: MedChemComm Vol. 1; no. 8; pp. 1488 - 1498
• Main Authors: Sharipova, Radmila R, Belenok, Mayya G, Garifullin, Bulat F, Sapunova, Anastasiya S, Voloshina, Alexandra D, Andreeva, Olga V, Strobykina, Irina Yu, Skvortsova, Polina V, Zuev, Yuriy F, Kataev, Vladimir E
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 01-08-2019
• Subjects: Anticancer properties; Apoptosis; Biotechnology; Cancer; Cytotoxicity; Glycoconjugates; Glycosides; Hepatocytes; Lead compounds; Liver; Mitochondria; Monosaccharides; Synthesis; Tamoxifen; Toxicity; Tumor cell lines; Viability
• ISSN: 2040-2503; 2040-2511; 2040-2511
• DOI: 10.1039/c9md00242a

A series of glycosides and glycoconjugates of diterpenoid isosteviol (16-oxo-
ent
-beyeran-19-oic acid) with various monosaccharide residues were synthesized and their cytotoxicity against some human cancer and normal cell lines was assayed. Most of the synthesized compounds demonstrated moderate to significant cytotoxicity against human cancer cell lines M-HeLa and MCF-7. Three lead compounds exhibited selective cytotoxic activities against M-HeLa (IC
50
= 10.0-15.1 μM) that were three times better than the cytotoxicity of the anti-cancer drug Tamoxifen (IC
50
= 28.0 μM). Moreover, the lead compounds were not cytotoxic with respect to the normal human cell line Chang liver (IC
50
> 100 μM), whereas Tamoxifen inhibited the viability of normal human Chang liver cells with an IC
50
value of 46.0 μM. It was determined that the cytotoxicity of the lead compounds was due to induction of apoptosis proceeding along the mitochondrial pathway. The cytotoxic activity of the synthesized compounds substantially depended on the nature of the monosaccharide residue and its position, that is, whether the monosaccharide residue was attached directly to the isosteviol skeleton or was moved away from it by means of a polymethylene linker.
A series of glycosides and glycoconjugates of diterpenoid isosteviol with various monosaccharide residues were synthesized. Most of them showed moderate to significant cytotoxicity against human cancer cell lines M-HeLa and MCF-7.