| Author | Ferreira, Sabrina B. | |
| Author | Sodero, Ana C. R. | |
| Author | Cardoso, Mariana F. C. | |
| Author | Lima, Emerson Silva | |
| Author | Kaiser, Carlos R. | |
| Author | Silva, Floriano P. | |
| Author | Ferreira, Vitor F. | |
| Access date | 2018-06-26T16:26:01Z | |
| Available date | 2018-06-26T16:26:01Z | |
| Document date | 2010 | |
| Citation | FERREIRA, Sabrina B. et al. Synthesis, Biological Activity, and Molecular Modeling Studies of 1H-1,2,3-Triazole Derivatives of Carbohydrates as r-Glucosidases Inhibitors. J. Med. Chem., v.53, p.2364-2375, 2010. | pt_BR |
| ISSN | 0022-2623 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/27118 | |
| Language | eng | pt_BR |
| Publisher | American Chemical Society | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Diabetes mellitus tipo 2 | pt_BR |
| Subject in Portuguese | Medicamentos | pt_BR |
| Title | Synthesis, biological activity, and molecular modeling studies of 1H-1,2,3-triazole derivatives of carbohydrates as alpha-glucosidases inhibitors | pt_BR |
| Type | Article | |
| DOI | 10.1021/jm901265h | |
| Abstract | A class of drugs in use for treating type II diabetes mellitus (T2D), typified by the pseudotetrasaccharide acarbose, act by inhibiting the alpha-glucosidase activity present in pancreatic secretions and in the brush border of the small intestine. Herein, we report the synthesis of a series of 4-substituted 1,2,3-triazoles conjugated with sugars, including D-xylose, D-galactose, D-allose, and D-ribose. Compounds were screened for alpha-glucosidase inhibitory activity using yeast maltase (MAL12) as a model enzyme. Methyl-2,3-O-isopropylidene-beta-D-ribofuranosides, such as the 4-(1-cyclohexenyl)-1,2,3-triazole derivative, were among the most active compounds, showing up to 25-fold higher inhibitory potency than the complex oligosaccharide acarbose. Docking studies on a MAL12 homology model disclosed a binding mode consistent with a transition-state-mimicking mechanism. Finally, the actual pharmacological potential of this triazole series was demonstrated by the reduction of postprandial blood glucose levels in normal rats. These compounds could represent new chemical scaffolds for developing novel drugs against T2D. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil / Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteínas e Peptídeos. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Amazonas. Faculdade de Ciências da Saúde. Manaus, AM, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteínas e Peptídeos. Rio de Janeiro, RJ. Brasil. | pt_BR |
| Affilliation | Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil. | pt_BR |
| Subject | type II diabetes mellitus | pt_BR |
| Subject | drugs | pt_BR |
| e-ISSN | 1520-4804 | |
| Embargo date | 2030-01-01 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
