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

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

Author Campo, Vanessa L. Google Scholar
Sesti-Costa, Renata Google Scholar
Carneiro, Zumira A. Google Scholar
Silva, Joao S. Google Scholar
Schenkman, Sergio Autor UNIFESP Google Scholar
Carvalho, Ivone Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract 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-N(3)-Gal (commercial), 6-N(3)-Gal, 3-N(3)-Glc and 3-N(3)-Gul with the corresponding alkyne-based 2-propynyl-sialic acid, as well as by click chemistry reaction between the amino acid N(3)-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 (IC(50) 260 mu M). 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. (C) 2011 Elsevier B.V. All rights reserved.
Keywords Triazole
Sialylmimetics
Click chemistry
Trypanosoma cruzi
trans-Sialidase
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2012-01-01
Published in Bioorganic & Medicinal Chemistry. Oxford: Pergamon-Elsevier B.V., v. 20, n. 1, p. 145-156, 2012.
ISSN 0968-0896 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 145-156
Origin http://dx.doi.org/10.1016/j.bmc.2011.11.022
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000298633300015
URI http://repositorio.unifesp.br/handle/11600/34338

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