| Title | Harnessing pyrrolidine iminosugars into dimeric structures for the rapid discovery of divalent glycosidase inhibitors |
|---|---|
| Authors | Carmona, Ana T. , Carrion-Jimenez, Sebastian , PINGITORE, VALERIA, Moreno-Clavijo, Elena , Robina, Inmaculada , Moreno-Vargas, Antonio J. |
| External publication | Si |
| Means | Eur. J. Med. Chem. |
| Scope | Article |
| Nature | Científica |
| JCR Quartile | 1 |
| SJR Quartile | 1 |
| JCR Impact | 4.833 |
| Publication date | 10/05/2018 |
| ISI | 000432640900052 |
| DOI | 10.1016/j.ejmech.2018.04.008 |
| Abstract | The synthesis of three libraries (1a-l, 1a\'-l\' and 2a-l) of dimeric iminosugars through CuAAC reaction between three different allcynyl pyrrolidines and a set of diazides was carried out. The resulting crude dimers were screened in situ against two a-fucosidases (libraries 1a-l and 2a\'-l\')\') and one fi-galactosidase (2a-l). This method is pioneer in the search of divalent glycosidase inhibitors. It has allowed the rapid identification of dimer 1i as the best inhibitor of alpha-fucosidases from bovine kidney (K-i = 0.15 nM) and Homo sapiens (K-i = 60 nM), and dimer 2e as the best inhibitor of beta-galactosidase from bovine liver (K-i = 5.8 mu M). In order to evaluate a possible divalent effect in the inhibition, the synthesis and biological analysis of the reference monomers were also performed. Divalent effect was only detected in the inhibition of bovine liver beta-galactosidase by dimer 2e. (C) 2018 Elsevier Masson SAS. All rights reserved. |
| Keywords | Iminosugars; Pyrrolidines; Click chemistry; In situ screening; alpha-Fucosidase inhibitors; beta-galactosidase inhibitors |
| Universidad Loyola members |