Synthesis and cytotoxicity of the conjugates of diterpenoid isosteviol and N-acetyl-D-glucosamine

• Published in: Natural product research Vol. 35; no. 8; pp. 1372 - 1378
• Main Authors: Garifullin, Bulat F., Strobykina, Irina Yu, Khabibulina, Leysan R., Sapunova, Anastasiya S., Voloshina, Aleksandra D., Sharipova, Radmila R., Khairutdinov, Bulat I., Zuev, Yuriy F., Kataev, Vladimir E.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-04-2021; Taylor & Francis Ltd
• Subjects: Acetylglucosamine - chemical synthesis; Acetylglucosamine - chemistry; Acetylglucosamine - pharmacology; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biotechnology; Cancer; Cell Line, Tumor; Conjugates; Cytotoxicity; Diterpenes; Diterpenes - chemical synthesis; Diterpenes - chemistry; Diterpenes - pharmacology; Diterpenes, Kaurane - chemical synthesis; Diterpenes, Kaurane - chemistry; Diterpenes, Kaurane - pharmacology; diterpenoids; Drug Screening Assays, Antitumor; Glucosamine; Hemolysis - drug effects; Hepatocytes; Humans; Inhibitory Concentration 50; isosteviol; Lead compounds; N-Acetyl-D-glucosamine; N-Acetylglucosamine; Structure-Activity Relationship; Tamoxifen; Toxicity; Tumor cell lines; diterpenoids; N-Acetyl-D-glucosamine; conjugates; isosteviol; cytotoxicity
• ISSN: 1478-6419; 1478-6427
• DOI: 10.1080/14786419.2019.1650355

A series of conjugates of diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) and N-acetyl-D-glucosamine was synthesised and their cytotoxicity against several human cancer cell lines (M-Hela, MCF-7, Hep G2, Panc-1, PC-3), as well as normal human cell lines (WI-38, Chang liver) was assayed. Most of the conjugates were found to be cytotoxic against the mentioned cancer cell lines in the range of IC
50
values 13-89 µM. Two lead compounds 14a and 14b showed selective cytotoxicity against M-Hela (IC
50
13 and 14 µM) that was two times as high as the cytotoxicity of the anti-cancer drug Tamoxifen in control (IC
50
28 µM). It was found that cytotoxic activity of the lead compounds against M-Hela cells is due to induction of apoptosis.