Design, synthesis and the effect of 1,2,3-triazole sialylmimetic neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase

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• 作者：Vanessa L. Campo^a ; Renata Sesti-Costa^b ; Zumira A. Carneiro^a ; Jo&atilde ; o S. Silva^b ; Sergio Schenkman^c ; Ivone Carvalho^a ; ^{carronal@usp.br}
• 关键词：Triazole ; Sialylmimetics ; Click chemistry ; Trypanosoma cruzi ; trans-Sialidase
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 出版时间：1 January, 2012
• 年：2012
• 卷：20
• 期：1
• 页码：145-156
• 全文大小：938 K

文摘

This work describes the synthesis of a series of sialylmimetic neoglycoconjugates represented by 1,4-disubstituted 1,2,3-triazole-sialic acid derivatives containing galactose modified at either C-1 or C-6 positions, glucose or gulose at C-3 position, and by the amino acid derivative 1,2,3-triazole fused threonine-3-O-galactose as potential TcTS inhibitors and anti-trypanosomal agents. This series was obtained by Cu(I)-catalysed azide-alkyne cycloaddition reaction (¡®click chemistry? between the azido-functionalized sugars 1-N₃-Gal (commercial), 6-N₃-Gal, 3-N₃-Glc and 3-N₃-Gul with the corresponding alkyne-based 2-propynyl-sialic acid, as well as by click chemistry reaction between the amino acid N₃-ThrOBn with 3-O-propynyl-GalOMe. The 1,2,3-triazole linked sialic acid-6-O-galactose and the sialic acid-galactopyranoside showed high Trypanosoma cruzi trans-sialidase (TcTS) inhibitory activity at 1.0 mM (approx. 90 % ), whilst only the former displayed relevant trypanocidal activity (IC₅₀ 260 ¦ÌM). These results highlight the 1,2,3-triazole linked sialic acid-6-O-galactose as a prototype for further design of new neoglycoconjugates against Chagas?disease.