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

• Type: Article in International Scientific Journal
• Date: 2021

Authors

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

Journal

Title: Acs Chemical Neuroscience

Vol. 12 No. 13

Pages: 3615-3624

ISSN: 1948-7193

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10