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

Clementina Manera, Giuseppe Saccomanni, Anna Maria Malfitano, Simone Bertini, Francesca Castelli, Chiara Laezza, Alessia Ligresti, Valentina Lucchesi, Tiziano Tuccinardi, Flavio Rizzolio, Maurizio Bifulco, Vincenzo Di Marzo, Antonio Giordano, Marco MacChia, Adriano Martinelli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)284-294
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume52
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Anti-proliferative
  • Cannabinoid
  • CB1 receptor
  • CB2 receptor

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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