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

Erika Lisztes, Erika Mező, Fruzsina Demeter, Lilla Horváth, Szilvia Bősze, Balázs István Tóth, Anikó Borbás, Mihály Herczeg

ChemMedChem 2021 May 06

filter terms:

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. © 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.

Citation

Erika Lisztes, Erika Mező, Fruzsina Demeter, Lilla Horváth, Szilvia Bősze, Balázs István Tóth, Anikó Borbás, Mihály Herczeg. Synthesis and Cell Growth Inhibitory Activity of Six Non-glycosaminoglycan-Type Heparin-Analogue Trisaccharides. ChemMedChem. 2021 May 06;16(9):1467-1476