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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells
Author
Gado, Francesca 1 ; Ferrisi, Rebecca 1   VIAFID ORCID Logo  ; Sarah Di Somma 2 ; Napolitano, Fabiana 2   VIAFID ORCID Logo  ; Mohamed, Kawthar A 3 ; Stevenson, Lesley A 4 ; Rapposelli, Simona 1   VIAFID ORCID Logo  ; Saccomanni, Giuseppe 1 ; Portella, Giuseppe 2   VIAFID ORCID Logo  ; Pertwee, Roger G 4 ; Laprairie, Robert B 5 ; Malfitano, Anna Maria 2   VIAFID ORCID Logo  ; Manera, Clementina 1 

 Department of Pharmacy, University of Pisa, 56126 Pisa, Italy; [email protected] (F.G.); [email protected] (R.F.); [email protected] (S.R.); [email protected] (G.S.) 
 Department of Translational Medical Sciences, University of Naples Federico II, 80131 Napoli, Italy; [email protected] (S.D.S.); [email protected] (F.N.); [email protected] (G.P.) 
 College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; [email protected] (K.A.M.); [email protected] (R.B.L.) 
 Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK; [email protected] (L.A.S.); [email protected] (R.G.P.) 
 College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; [email protected] (K.A.M.); [email protected] (R.B.L.); Department of Pharmacology, College of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada 
First page
3019
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
14203049
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2663046699
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.