Design, Synthesis, and Biological Evaluation of Hybrid Glypromate Analogues Using 2-Azanorbornane as a Prolyl and Pipecolyl Surrogate
| Autor: | Ivo E. Sampaio-Dias, Miguel Santejo, José E. Rodríguez-Borges, Cristina Alcoholado, Manuel Algarra, Sara C. Silva-Reis, Xerardo García-Mera, Márcia A. Liz |
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| Rok vydání: | 2021 |
| Předmět: |
Physiology
business.industry Peptidomimetic Cognitive Neuroscience Mesenchymal stem cell Adipose tissue Neurodegenerative Diseases Cell Biology General Medicine Pharmacology medicine.disease Biochemistry Neuroprotection Neuroblastoma Neuroprotective Drugs Neuroprotective Agents medicine Humans Inducer business Oligopeptides Glypromate |
| Zdroj: | ACS chemical neuroscience. 12(19) |
| ISSN: | 1948-7193 |
| Popis: | Neurodegenerative disorders of the central nervous system are a class of heterogeneous pathologies affecting millions of people worldwide and represent a global health burden in developed and developing countries. Without restorative treatments currently available, research on neuroprotective drugs is considered a health priority. In this study, new analogues of the glycyl-l-prolyl-l-glutamic acid (Glypromate) neuropeptide were designed, synthesized, and biologically evaluated using (1R,3S,4S)-2-azanorbornane-3-carboxylic acid as a hybrid construct of l-proline and l-pipecolic acid. Neuroprotection assays carried out in human neuroblastoma SH-SY5Y cells using 6-hydroxydopamine as a stress inducer showed great percentage of recovery (29.7-40.0%) at 100 μM. Among this series, [(1R,3S,4S)-2-glycyl-2-azanorbornane-3-carbonyl]-l-aspartic acid (2a) stands out with a remarkable percentage of recovery (40.0%, at 100 μM) and safe toxicological profile in SH-SY5Y and human adipose mesenchymal stem cells. |
| Databáze: | OpenAIRE |
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