Synthesis and cell growth inhibitory activity of six non-glycosaminoglycan‐type heparin‐analogue trisaccharides

Lisztes, Erika and Mező, Erika and Demeter, Fruzsina and Horváth, Lilla and Bősze, Szilvia and Tóth, Balázs István and Borbás, Anikó and Herczeg, Mihály (2021) Synthesis and cell growth inhibitory activity of six non-glycosaminoglycan‐type heparin‐analogue trisaccharides. CHEMMEDCHEM, 16 (9). pp. 1467-1476. ISSN 1860-7179 (print); 1860-7187 (online)

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Abstract

The design and synthesis of heparin mimetics with high anticancer activity but no anticoagulant activity is an important task in medicinal chemistry. Here, 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 cell growth inhibitory effects on ovary carcinoma (A2780) and melanoma (WM35) cells. Methyl substituents on the glucuronide unit proved to be detrimental while acetyl substituents were beneficial to the cytostatic activity of the sulfated derivatives.

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