Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells

Autor: Francesca Gado, Rebecca Ferrisi, Sarah Di Somma, Fabiana Napolitano, Kawthar A. Mohamed, Lesley A. Stevenson, Simona Rapposelli, Giuseppe Saccomanni, Giuseppe Portella, Roger G. Pertwee, Robert B. Laprairie, Anna Maria Malfitano, Clementina Manera
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecules, Vol 27, Iss 9, p 3019 (2022)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules27093019
Popis: 1,8-naphthyridine-3-carboxamide structures were previously identified as a promising scaffold from which to obtain CB2R agonists with anticancer and anti-inflammatory activity. This work describes the synthesis and functional characterization of new 1,8-naphthyridin-2(1H)-one-3-carboxamides with high affinity and selectivity for CB2R. The new compounds were able to pharmacologically modulate the cAMP response without modulating CB2R-dependent β-arrestin2 recruitment. These structures were also evaluated for their anti-cancer activity against SH-SY5Y and SK-N-BE cells. They were able to reduce the cell viability of both neuroblastoma cancer cell lines with micromolar potency (IC50 of FG158a = 11.8 μM and FG160a = 13.2 μM in SH-SY5Y cells) by a CB2R-mediated mechanism. Finally, in SH-SY5Y cells one of the newly synthesized compounds, FG158a, was able to modulate ERK1/2 expression by a CB2R-mediated effect, thus suggesting that this signaling pathway might be involved in its potential anti-cancer effect.
Databáze: Directory of Open Access Journals
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