Synthesis and Cell Growth Inhibitory Activity of Six Non‐glycosaminoglycan‐Type Heparin‐Analogue Trisaccharides

Autor: Lisztes, Erika, Mező, Erika, Demeter, Fruzsina, Horváth, Lilla, Bősze, Szilvia, István Tóth, Balázs, Borbás, Anikó, Herczeg, Mihály
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Chemmedchem
ISSN: 1860-7187
1860-7179
Popis: The design and synthesis of heparin mimetics with high anticancer activity but no anticoagulant activity is an important task in medicinal chemistry. Herein, we present the efficient synthesis of five Glc‐GlcA‐Glc‐sequenced and one Glc‐IdoA‐Glc‐sequenced non‐glycosaminoglycan, heparin‐related trisaccharides with various sulfation/sulfonylation and methylation patterns. The cell growth inhibitory effects of the compounds were tested against four cancerous human cell lines and two non‐cancerous cell lines. Two d‐glucuronate‐containing tetra‐O‐sulfated, partially methylated trisaccharides displayed remarkable and selective inhibitory effects on the growth of ovary carcinoma (A2780) and melanoma (WM35) cells. Methyl substituents on the glucuronide unit proved to be detrimental, whereas acetyl substituents were beneficial to the cytostatic activity of the sulfated derivatives.
Better off without Me: Six uronic acid‐containing sulfated and sulfonylated trisaccharides have been prepared, and their cell growth inhibitory effects have been evaluated on cancerous and non‐cancerous cell lines. Two glucuronate‐containing sulfated trisaccharides selectively inhibited the cell growth of two cancerous human cell lines. Methyl substituents on the glucuronate unit were found to be detrimental to the cytostatic activity.
Databáze: OpenAIRE
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