Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase

Intranuovo, F.; Brunetti, L.; Delre, P.; Mangiatordi, G.F.; Stefanachi, A.; Laghezza, A.; Niso, M.; Leonetti, F.; Loiodice, F.; Ligresti, A.; Kostrzewa, M.; Brea Floriani, José Manuel; Loza García, María Isabel; Sotelo, E.; Saviano, M.; Colabufo, N.A.; Riganti, C.; Abate, C.; Contino, M.

Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase

Cannabinoid type 2 receptor (CB2R), belonging to the endocannabinoid system, is overexpressed in pathologies characterized by inflammation, and its activation counteracts inflammatory states. Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the degradation of the main endocannabinoid a...

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Autores:	Intranuovo, F., Brunetti, L., Delre, P., Mangiatordi, G.F., Stefanachi, A., Laghezza, A., Niso, M., Leonetti, F., Loiodice, F., Ligresti, A., Kostrzewa, M., Brea Floriani, José Manuel, Loza García, María Isabel, Sotelo, E., Saviano, M., Colabufo, N.A., Riganti, C., Abate, C., Contino, M.
Tipo de recurso:	artículo
Fecha de publicación:	2023
País:	España
Institución:	Servizo Galego de Saúde (SERGAS)
Repositorio:	RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:	oai:runa.sergas.gal:20.500.11940/21397
Acceso en línea:	https://portalcientifico.sergas.gal//documentos/63b996df4386723d2da378bb http://hdl.handle.net/20.500.11940/21397
Access Level:	acceso abierto
Palabra clave:	Cannabinoids Endocannabinoids Receptor, Cannabinoid, CB2 Molecular Docking Simulation Benzamides Anti-Inflammatory Agents Amidohydrolases Cannabinoid Receptor Agonists Receptor, Cannabinoid, CB1 AS Santiago IDIS

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network_acronym_str	ES
network_name_str	España
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spelling	Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide HydrolaseIntranuovo, F.Brunetti, L.Delre, P.Mangiatordi, G.F.Stefanachi, A.Laghezza, A.Niso, M.Leonetti, F.Loiodice, F.Ligresti, A.Kostrzewa, M.Brea Floriani, José ManuelLoza García, María IsabelSotelo, E.Saviano, M.Colabufo, N.A.Riganti, C.Abate, C.Contino, M.CannabinoidsEndocannabinoidsReceptor, Cannabinoid, CB2Molecular Docking SimulationBenzamidesAnti-Inflammatory AgentsAmidohydrolasesCannabinoid Receptor AgonistsReceptor, Cannabinoid, CB1AS SantiagoIDISCannabinoid type 2 receptor (CB2R), belonging to the endocannabinoid system, is overexpressed in pathologies characterized by inflammation, and its activation counteracts inflammatory states. Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the degradation of the main endocannabinoid anandamide; thus, the simultaneous CB2R activation and FAAH inhibition may be a synergistic anti-inflammatory strategy. Encouraged by principal component analysis (PCA) data identifying a wide chemical space shared by CB2R and FAAH ligands, we designed a small library of adamantyl-benzamides, as potential dual agents, CB2R agonists, and FAAH inhibitors. The new compounds were tested for their CB2R affinity/selectivity and CB2R and FAAH activity. Derivatives 13, 26, and 27, displaying the best pharmacodynamic profile as CB2R full agonists and FAAH inhibitors, decreased pro-inflammatory and increased anti-inflammatory cytokines production. Molecular docking simulations complemented the experimental findings by providing a molecular rationale behind the observed activities. These multitarget ligands constitute promising anti-inflammatory agents.2023info:eu-repo/semantics/articlehttps://portalcientifico.sergas.gal//documentos/63b996df4386723d2da378bbhttp://hdl.handle.net/20.500.11940/21397reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttps://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/213972026-06-12T08:40:47Z
dc.title.none.fl_str_mv	Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase
title	Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase
spellingShingle	Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase Intranuovo, F. Cannabinoids Endocannabinoids Receptor, Cannabinoid, CB2 Molecular Docking Simulation Benzamides Anti-Inflammatory Agents Amidohydrolases Cannabinoid Receptor Agonists Receptor, Cannabinoid, CB1 AS Santiago IDIS
title_short	Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase
title_full	Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase
title_fullStr	Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase
title_full_unstemmed	Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase
title_sort	Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase
dc.creator.none.fl_str_mv	Intranuovo, F. Brunetti, L. Delre, P. Mangiatordi, G.F. Stefanachi, A. Laghezza, A. Niso, M. Leonetti, F. Loiodice, F. Ligresti, A. Kostrzewa, M. Brea Floriani, José Manuel Loza García, María Isabel Sotelo, E. Saviano, M. Colabufo, N.A. Riganti, C. Abate, C. Contino, M.
author	Intranuovo, F.
author_facet	Intranuovo, F. Brunetti, L. Delre, P. Mangiatordi, G.F. Stefanachi, A. Laghezza, A. Niso, M. Leonetti, F. Loiodice, F. Ligresti, A. Kostrzewa, M. Brea Floriani, José Manuel Loza García, María Isabel Sotelo, E. Saviano, M. Colabufo, N.A. Riganti, C. Abate, C. Contino, M.
author_role	author
author2	Brunetti, L. Delre, P. Mangiatordi, G.F. Stefanachi, A. Laghezza, A. Niso, M. Leonetti, F. Loiodice, F. Ligresti, A. Kostrzewa, M. Brea Floriani, José Manuel Loza García, María Isabel Sotelo, E. Saviano, M. Colabufo, N.A. Riganti, C. Abate, C. Contino, M.
author2_role	author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Cannabinoids Endocannabinoids Receptor, Cannabinoid, CB2 Molecular Docking Simulation Benzamides Anti-Inflammatory Agents Amidohydrolases Cannabinoid Receptor Agonists Receptor, Cannabinoid, CB1 AS Santiago IDIS
topic	Cannabinoids Endocannabinoids Receptor, Cannabinoid, CB2 Molecular Docking Simulation Benzamides Anti-Inflammatory Agents Amidohydrolases Cannabinoid Receptor Agonists Receptor, Cannabinoid, CB1 AS Santiago IDIS
description	Cannabinoid type 2 receptor (CB2R), belonging to the endocannabinoid system, is overexpressed in pathologies characterized by inflammation, and its activation counteracts inflammatory states. Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the degradation of the main endocannabinoid anandamide; thus, the simultaneous CB2R activation and FAAH inhibition may be a synergistic anti-inflammatory strategy. Encouraged by principal component analysis (PCA) data identifying a wide chemical space shared by CB2R and FAAH ligands, we designed a small library of adamantyl-benzamides, as potential dual agents, CB2R agonists, and FAAH inhibitors. The new compounds were tested for their CB2R affinity/selectivity and CB2R and FAAH activity. Derivatives 13, 26, and 27, displaying the best pharmacodynamic profile as CB2R full agonists and FAAH inhibitors, decreased pro-inflammatory and increased anti-inflammatory cytokines production. Molecular docking simulations complemented the experimental findings by providing a molecular rationale behind the observed activities. These multitarget ligands constitute promising anti-inflammatory agents.
publishDate	2023
dc.date.none.fl_str_mv	2023
dc.type.none.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://portalcientifico.sergas.gal//documentos/63b996df4386723d2da378bb http://hdl.handle.net/20.500.11940/21397
url	https://portalcientifico.sergas.gal//documentos/63b996df4386723d2da378bb http://hdl.handle.net/20.500.11940/21397
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.rights.none.fl_str_mv	https://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.source.none.fl_str_mv	reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas instname:Servizo Galego de Saúde (SERGAS)
instname_str	Servizo Galego de Saúde (SERGAS)
reponame_str	RUNA. Repositorio da Consellería de Sanidade e Sergas
collection	RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,811543

Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase

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