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

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 trisac...

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Autores principales: Lisztes, Erika, Mező, Erika, Demeter, Fruzsina, Horváth, Lilla, Bősze, Szilvia, István Tóth, Balázs, Borbás, Anikó, Herczeg, Mihály
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247843/
https://www.ncbi.nlm.nih.gov/pubmed/33433040
http://dx.doi.org/10.1002/cmdc.202000917
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author Lisztes, Erika
Mező, Erika
Demeter, Fruzsina
Horváth, Lilla
Bősze, Szilvia
István Tóth, Balázs
Borbás, Anikó
Herczeg, Mihály
author_facet Lisztes, Erika
Mező, Erika
Demeter, Fruzsina
Horváth, Lilla
Bősze, Szilvia
István Tóth, Balázs
Borbás, Anikó
Herczeg, Mihály
author_sort Lisztes, Erika
collection PubMed
description 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.
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spelling pubmed-82478432021-07-02 Synthesis and Cell Growth Inhibitory Activity of Six Non‐glycosaminoglycan‐Type Heparin‐Analogue Trisaccharides Lisztes, Erika Mező, Erika Demeter, Fruzsina Horváth, Lilla Bősze, Szilvia István Tóth, Balázs Borbás, Anikó Herczeg, Mihály ChemMedChem Full Papers 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. John Wiley and Sons Inc. 2021-02-12 2021-05-06 /pmc/articles/PMC8247843/ /pubmed/33433040 http://dx.doi.org/10.1002/cmdc.202000917 Text en © 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Full Papers
Lisztes, Erika
Mező, Erika
Demeter, Fruzsina
Horváth, Lilla
Bősze, Szilvia
István Tóth, Balázs
Borbás, Anikó
Herczeg, Mihály
Synthesis and Cell Growth Inhibitory Activity of Six Non‐glycosaminoglycan‐Type Heparin‐Analogue Trisaccharides
title Synthesis and Cell Growth Inhibitory Activity of Six Non‐glycosaminoglycan‐Type Heparin‐Analogue Trisaccharides
title_full Synthesis and Cell Growth Inhibitory Activity of Six Non‐glycosaminoglycan‐Type Heparin‐Analogue Trisaccharides
title_fullStr Synthesis and Cell Growth Inhibitory Activity of Six Non‐glycosaminoglycan‐Type Heparin‐Analogue Trisaccharides
title_full_unstemmed Synthesis and Cell Growth Inhibitory Activity of Six Non‐glycosaminoglycan‐Type Heparin‐Analogue Trisaccharides
title_short Synthesis and Cell Growth Inhibitory Activity of Six Non‐glycosaminoglycan‐Type Heparin‐Analogue Trisaccharides
title_sort synthesis and cell growth inhibitory activity of six non‐glycosaminoglycan‐type heparin‐analogue trisaccharides
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247843/
https://www.ncbi.nlm.nih.gov/pubmed/33433040
http://dx.doi.org/10.1002/cmdc.202000917
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