Design, Synthesis, and Biological Evaluation of Hybrid Glypromate Analogues Using 2-Azanorbornane as a Prolyl and Pipecolyl Surrogate

• Tipo: Artigo em Revista Científica Internacional
• Data: 2021

Autores

Sampaio Dias, IE (Autor) Outra; Santejo, M (Autor) Outra; Silva Reis, SC (Autor) Outra; Liz, MA (Autor) Outra; Alcoholado, C (Autor) Outra; Algarra, M (Autor) Outra; Garcia Mera, X (Autor) Outra; Rodriguez Borges, JE (Autor) FCUP

Revista

Título: Acs Chemical Neuroscience

Vol. 12 Nº 13

Páginas: 3615-3624

ISSN: 1948-7193

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 2 Citações

Scopus - 2 Citações

Outras Informações

ID Authenticus: P-00V-D24

DOI: 10.1021/acschemneuro.1c00339

Abstract (EN): 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-Lprolyl-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 mu M. 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 mu M) and safe toxicological profile in SH-SY5Y and human adipose mesenchymal stem cells.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10