Design, synthesis, binding, and molecular modeling studies of new potent ligands of cannabinoid receptors

Antonella Brizzi*, Maria Grazia Cascio, Vittorio Brizzi, Tiziana Bisogno, Maria Teresa Dinatolo, Adriano Martinelli, Tiziano Tuccinardi, Vincenzo Di Marzo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

In our ongoing program aimed at the design, synthesis, and biological evaluation of novel cannabinoid receptor ligands derived from olivetol and hexyl-resorcinol, we have designed a structural model for new derivatives on the basis of a previous study. Here we report the synthesis, binding, and molecular modeling studies of new potent compounds with high affinity toward CB1 and CB2 receptors. Compounds with amidic 'heads' with alkyloxy chains varying in length from 8 to 12 carbon atoms showed nanomolar affinity for both receptors, depending on the type of aromatic backbone. Two of the new compounds, although not very potent, exhibit selectivity for CB1 receptors (CB1/CB2 = 0.07 and 0.08, respectively). Molecular modeling studies fitted this new class of cannabinoid ligands into a CB1 receptor model, and the qualitative analysis of the results was in general agreement with the CB1 affinity constants observed experimentally for these derivatives.

Original languageEnglish
Pages (from-to)5406-5416
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number16
Early online date31 May 2007
DOIs
Publication statusPublished - 15 Aug 2007

Bibliographical note

Funding Information:
We thank MIUR (PRIN 2004037521) and the Università degli Studi di Siena, Italy, for financial support. We thank Mr. Marco Allarà for technical assistance with assays.

Keywords

  • Anandamide
  • Cannabinoid receptors
  • Docking
  • Endocannabinoids

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