title: Rational design, synthesis and anti-proliferative properties of new CB2 selective cannabinoid receptor ligands: an investigation of the 1,8-naphthyridin-2(1H)-one scaffold.
abstract: CB2 receptor ligands are becoming increasingly attractive drugs due to the potential role of this receptor in several physiopathological processes. Using our previously described series of 1,8-naphthyridin-2(1H)-on-3-carboxamides as a lead class, several nitrogen heterocyclic derivatives, characterized by different central cores, were synthesized and tested for their affinity toward the human CB1 and CB2 cannabinoid receptors. The obtained results suggest that the new series of quinolin-2(1H)-on-3-carboxamides, 4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamides and 1,2-dihydro-2-oxopyridine-3-carboxamides represent novel scaffolds very suitable for the development of promising CB2 ligands. Furthermore, the newly synthesized CB2 ligands inhibit proliferation of several cancer cell lines. In particular, it was demonstrated that in DU-145 cell line these ligands exert a CB2-mediated anti-proliferative action and decrease the CB2 receptor expression levels.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126 Pisa, Italy. manera@farm.unipi.it
authors.forename: Clementina
authors.initials: C
authors.lastname: Manera
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saccomanni
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Malfitano
authors.forename: Simone
authors.initials: S
authors.lastname: Bertini
authors.forename: Francesca
authors.initials: F
authors.lastname: Castelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Laezza
authors.forename: Alessia
authors.initials: A
authors.lastname: Ligresti
authors.forename: Valentina
authors.initials: V
authors.lastname: Lucchesi
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.forename: Flavio
authors.initials: F
authors.lastname: Rizzolio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bifulco
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
authors.forename: Adriano
authors.initials: A
authors.lastname: Martinelli
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: C574518:1,8-naphthyridin-2(1H)-one; D000970:Antineoplastic Agents; D008024:Ligands; D009287:Naphthyridines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2