期刊
CHEMMEDCHEM
卷 16, 期 9, 页码 1467-1476出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.202000917
关键词
antitumor activity; heparin; human cells; synthesis; trisaccharides
资金
- Premium Postdoctoral Program of HAS [PPD 461038]
- EU
- European Regional Development Fund [GINOP-2.3.2-15-2016-00008]
- National Research, Development and Innovation Office of Hungary [K128368, PD134791]
- Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences
- New National Excellence Program of the Ministry for Innovation and Technology [uNKP-20-5-DE-422]
- ELTE Thematic Excellence Programme2020 - National Research, Development and Innovation Office [TKP2020-IKA-05]
The study focused on synthesizing non-glycosaminoglycan, heparin-related trisaccharides with high anticancer activity. Partially methylated compounds showed significant inhibitory effects on ovarian carcinoma and melanoma cells, while acetyl substituents were beneficial to cytostatic activity of the sulfated derivatives.
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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