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

Autor: Gado F; Department of Pharmacy, University of Pisa, 56126 Pisa, Italy., Ferrisi R; Department of Pharmacy, University of Pisa, 56126 Pisa, Italy., Di Somma S; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Napoli, Italy., Napolitano F; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Napoli, Italy., Mohamed KA; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada., Stevenson LA; Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK., Rapposelli S; Department of Pharmacy, University of Pisa, 56126 Pisa, Italy., Saccomanni G; Department of Pharmacy, University of Pisa, 56126 Pisa, Italy., Portella G; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Napoli, Italy., Pertwee RG; Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK., Laprairie RB; College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.; Department of Pharmacology, College of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada., Malfitano AM; Department of Translational Medical Sciences, University of Naples Federico II, 80131 Napoli, Italy., Manera C; Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2022 May 07; Vol. 27 (9). Date of Electronic Publication: 2022 May 07.
DOI: 10.3390/molecules27093019
Abstrakt: 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(1 H )-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 (IC 50 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: MEDLINE
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