Scouting new sigma receptor ligands: Synthesis, pharmacological evaluation and molecular modeling of 1,3-dioxolane-based structures and derivatives
Articolo
Data di Pubblicazione:
2016
Citazione:
Scouting new sigma receptor ligands: Synthesis, pharmacological evaluation and molecular modeling of 1,3-dioxolane-based structures and derivatives / S. Franchini, U.M. Battisti, A. Prandi, A. Tait, C. Borsari, E. Cichero, P. Fossa, A. Cilia, O. Prezzavento, S. Ronsisvalle, G. Arico, C. Parenti, L. Brasili. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 112:(2016 Apr 13), pp. 1-19. [10.1016/j.ejmech.2016.01.059]
Abstract:
Herein we report the synthesis and biological activity of new sigma receptor (σR) ligands obtained by combining different substituted five-membered heterocyclic rings with appropriate σR pharmacophoric amines. Radioligand binding assay, performed on guinea pig brain membranes, identified 25b (1-(1,4-dioxaspiro[4.5]decan-2-ylmethyl)-4-benzylpiperazine) as the most interesting compound of the series, displaying high affinity and selectivity for σ1R (pKiσ1 = 9.13; σ1/σ2 = 47). The ability of 25b to modulate the analgesic effect of the κ agonist (-)-U-50,488H and μ agonist morphine was evaluated in vivo by radiant heat tail-flick test. It exhibited anti-opioid effects on both κ and μ receptor-mediated analgesia, suggesting an agonistic behavior at σ1R. Docking studies were performed on the theoretical σ1R homology model. The present work represents a new starting point for the design of more potent and selective σ1R ligands.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
1,3-Dioxolane; Piperazine; Piperidine; Receptor-mediated analgesia; Sigma receptors ligands; Sigma-1; Sigma-2
Elenco autori:
S. Franchini, U.M. Battisti, A. Prandi, A. Tait, C. Borsari, E. Cichero, P. Fossa, A. Cilia, O. Prezzavento, S. Ronsisvalle, G. Arico, C. Parenti, L. Brasili
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