Design, synthesis and biological evaluation of peptide derivatives of L-dopa as anti-parkinsonian agents.

Abstract

A series of dipeptide derivatives of L-dopa were synthesized and investigated for their pharmacological activity using the unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat as an experimental model of Parkinson's disease. Among them, (S)-isopropyl 2-(2-amino-2-methylpropanamido)-3-(3,4-dihydroxyphenyl)propanoate (4 g) was found to be the most active compound, with 106% AUC activity and 149% peak activity of L-dopa after oral administration.

• Authors: Tao Zhou, Robert C Hider, Peter Jenner, Bruce Campbell, Christopher J Hobbs, Sarah Rose, Mark Jairaj, Kayhan A Tayarani-Binazir, Alexander Syme
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 19 Pg. 5279-82 (Oct 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 23973169 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antiparkinson Agents
• Dipeptides
• Peptides
• isopropyl 2-(2-amino-2-methylpropanamido)-3-(3,4-dihydroxyphenyl)propanoate
• Levodopa

Topics

• Animals
• Antiparkinson Agents (administration & dosage, chemical synthesis, pharmacology)
• Dipeptides (administration & dosage, chemical synthesis, pharmacology)
• Disease Models, Animal
• Drug Design
• Levodopa (administration & dosage, analogs & derivatives, chemical synthesis, pharmacology)
• Male
• Molecular Structure
• Motor Activity (drug effects)
• Peptides (administration & dosage, chemical synthesis, pharmacology)
• Rats
• Rats, Wistar