Tuning of β-glucosidase and α-galactosidase inhibition by generation and in situ screening of a library of pyrrolidine-triazole hybrid molecules
The preliminary screening of two libraries of epimeric (pyrrolidin-2-yl)triazoles (14a-s and 22a-s), generated via click chemistry, allowed the rapid identification of four α-galactosidase (coffee beans) inhibitors (22b,k,p,r) and two β-glucosidase (almond) inhibitors (14b,f) in the low μM range. Th...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/166595 |
| Acceso en línea: | https://hdl.handle.net/11441/166595 https://doi.org/10.1016/j.ejmech.2017.06.055 |
| Access Level: | acceso abierto |
| Palabra clave: | iminosugars glycosidase inhibitors pyrrolidines triazole click reaction |
| Sumario: | The preliminary screening of two libraries of epimeric (pyrrolidin-2-yl)triazoles (14a-s and 22a-s), generated via click chemistry, allowed the rapid identification of four α-galactosidase (coffee beans) inhibitors (22b,k,p,r) and two β-glucosidase (almond) inhibitors (14b,f) in the low μM range. The additional biological analysis of 14b,f towards β-glucocerebrosidase (human lysosomal β-glucosidase), as target enzyme for Gaucher disease, showed a good correlation with the inhibition results obtained for the plant (almond) enzyme. Surprisingly, although these compounds showed inhibition towards β-glucocerebrosidase as acid hydrolase, they did not inhibit bovine liver β-glucosidase as neutral hydrolase. In contrast to what was observed for β-glucosidase inhibition, the coffee beans α-galactosidase inhibitors of the epimeric library (22b,k,p,r) only showed weak inhibition towards human lysosomal α-galactosidase. |
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