Synthesis, characterization and evaluation of anti-hyperalgesia, anticonvulsant and antioxidant activity of novel VV-hemorphin-5 analogs.

Autor: Todorov P; Department of Organic Chemistry, University of Chemical Technology and Metallurgy, Sofia, Bulgaria., Georgieva S; Department of Analytical Chemistry, University of Chemical Technology and Metallurgy, Sofia, Bulgaria., Tchekalarova J; Department of Organic Chemistry, University of Chemical Technology and Metallurgy, Sofia, Bulgaria.; Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria., Peneva P; Department of Organic Chemistry, University of Chemical Technology and Metallurgy, Sofia, Bulgaria., Mateeva P; Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria., Assenov B; Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.; Faculty of Medicine, Sofia University 'St. Kliment Ohridski', Sofia, Bulgaria., Dzhambazova E; Faculty of Medicine, Sofia University 'St. Kliment Ohridski', Sofia, Bulgaria., Pechlivanova D; Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.; Faculty of Medicine, Sofia University 'St. Kliment Ohridski', Sofia, Bulgaria.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2023 Oct; Vol. 356 (10), pp. e2300267. Date of Electronic Publication: 2023 Aug 02.
DOI: 10.1002/ardp.202300267
Abstrakt: Two series of new VV-hemorphin-5 analogs with structures Val-Val-Tyr-Xxx-Trp-Thr-Gln-NH 2 and Adam-Val-Val-Tyr-Xxx-Trp-Thr-Gln-NH 2 , where Xxx is Ac5c (1-aminocyclopentane-1-carboxylic acid), Ac6c (1-aminocyclohexane-1-carboxylic acid), Ac7c (1-aminocycloheptane-1-carboxylic acid), and Adam is the low-molecular-weight lipophilic adamantyl building block, were synthesized, characterized electrochemically and evaluated for antioxidant, anti-hyperalgesia, and anticonvulsant activity. The design of the compounds followed the strategy to improve the propensity for aqueous solubility and/or to increase their affinity for the target receptor or enzyme. The partition coefficient value shows that the peptide scaffold goes from hydrophilic to lipophilic with the increasing size of the cycloalkane ring and even more with the introduction of the adamantane. The peptides C5-V and C7-V were the only analogs that provoked an immediate antinociceptive effect changing the mechanical pain threshold. The six new peptide analogs produced a significant and long-lasting carrageenan model of inflammatory pain in rats. While the adamantane hemorphin analog Ad7-V was the only compound with the potency to suppress psychomotor seizures in the 6-Hz test, the C6-V and Ad6-V exhibited protective activity against the seizure spread in the maximal electroshock seizure test in mice. The active analogs did not show neurotoxicity or sedative effects. Our results revealed a structure-related specific activity of a newly designed hemorphin analog that could be used as a template for future modification and preparation of compounds with potential analgesic and anticonvulsant activity.
(© 2023 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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