|
|||||
|
|
Synthesis and Cell Growth Inhibitory Activity of Six Non-glycosaminoglycan-Type Heparin-Analogue Trisaccharides |
|
| Authors: | Dr. Erika Lisztes Dr. Erika Mező Fruzsina Demeter Lilla Horváth Dr. Szilvia Bősze Dr. Balázs István Tóth Prof. Anikó Borbás Dr. Mihály Herczeg |
| Affiliation: | 1. Department of Physiology, University of Debrecen PO Box 22, 4012 Debrecen, Hungary;2. Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem tér 1, 4032 Debrecen, Hungary;3. Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem tér 1, 4032 Debrecen, Hungary Doctoral School of Chemistry, University of Debrecen, Egyetem tér 1, 4032 Debrecen, Hungary MTA-DE Molecular Recognition and Interaction Research Group, ELKH, University of Debrecen, Egyetem tér 1, 4032 Debrecen, Hungary;4. MTA-ELTE Research Group of Peptide Chemistry, Eötvös Loránd University, Pázmány Péter sétány 1/a, 1117 Budapest, Hungary |
| Abstract: | 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. |
| Keywords: | antitumor activity heparin human cells synthesis trisaccharides |