Design, synthesis and enzymatic evaluation of 3-O-substituted aryl ß-D-galactopyranosides as inhibitors of Trypanosoma cruzi trans-sialidase.
Bioorg Med Chem Lett
; 24(18): 4529-4532, 2014 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-25149510
ABSTRACT
The trans-sialidase of Trypanosoma cruzi (TcTS) is a surface enzyme that modifies the parasite glycocalyx covering it with sialic acid. This process is essential to adhesion and invasion mechanisms in life cycle of the protozoan in the human host, making TcTS a very attractive molecular target for drug design. Using the TcTS substrate 3'-sialyllactose as prototype, D-galactose-derived potential inhibitors of TcTS were designed using strategies of molecular modification. Ten new aryl galactosides modified at carbon-3 were synthesized employing classical carbohydrate chemistry and dibutyltin oxide method for regioselective 3-O-alkylations and evaluated against TcTS by spectrofluorimetry. The 4-methoxycarbonyl-2-nitrophenyl 3-O-carboxymethyl-ß-D-galactopyranoside was the most active compound inhibiting 21% of TcTS enzymatic activity at 1 mM.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trypanosoma cruzi
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Glicoproteínas
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Desenho de Fármacos
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Inibidores Enzimáticos
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Galactose
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Neuraminidase
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article