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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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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. |
format | Online Article Text |
id | pubmed-8247843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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