Synthesis and biological evaluation of several structural analogs of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand

Yoshitomo Suhara, Saori Oka, Atsushi Kittaka, Hiroaki Takayama, Keizo Waku, Takayuki Sugiura

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

2-Arachidonoylglycerol (2-AG (1)) is an endogenous ligand for the cannabinoid receptors (CB1 and CB2). There is growing evidence that 2-arachidonoylglycerol plays important physiological and pathophysiological roles in various mammalian tissues and cells, though the details remain to be clarified. In this study, we synthesized several remarkable analogs of 2-arachidonoylglycerol, closely related in chemical structure to 2-arachidonoylglycerol: an analog containing an isomer of arachidonic acid with migrated olefins (2-AGA118 (3)), an analog containing a one-carbon shortened fatty acyl moiety (2-AGA113 (4)), an analog containing an one-carbon elongated fatty acyl moiety (2-AGA114 (5)), a hydroxy group-containing analog (2-AGA105 (6)), a ketone group-containing analog (2-AGA109 (7)), and a methylene-linked analog (2-AGA104 (8)). We evaluated their biological activities as cannabinoid receptor agonists using NG108-15 cells which express the CB1 receptor and HL-60 cells which express the CB2 receptor. Notably, these structural analogs of 2-arachidonoylglycerol exhibited only weak agonistic activities toward either the CB1 receptor or the CB2 receptor, which is in good contrast to 2-arachidonoylglycerol which acted as a full agonist at these cannabinoid receptors. These results clearly indicate that the structure of 2-arachidonoylglycerol is strictly recognized by the cannabinoid receptors (CB1 and CB2) and provide further evidence that the cannabinoid receptors are primarily the intrinsic receptors for 2-arachidonoylglycerol.

Original languageEnglish
Pages (from-to)854-867
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number2
DOIs
Publication statusPublished - 2007 Jan 15
Externally publishedYes

Fingerprint

Cannabinoid Receptors
Cannabinoid Receptor CB2
Ligands
Cannabinoid Receptor CB1
Carbon
Cannabinoid Receptor Agonists
2-arachidonylglycerol
Alkenes
Bioactivity
Ketones
Arachidonic Acid
Isomers
Tissue

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Synthesis and biological evaluation of several structural analogs of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand. / Suhara, Yoshitomo; Oka, Saori; Kittaka, Atsushi; Takayama, Hiroaki; Waku, Keizo; Sugiura, Takayuki.

In: Bioorganic and Medicinal Chemistry, Vol. 15, No. 2, 15.01.2007, p. 854-867.

Research output: Contribution to journalArticle

Suhara, Yoshitomo ; Oka, Saori ; Kittaka, Atsushi ; Takayama, Hiroaki ; Waku, Keizo ; Sugiura, Takayuki. / Synthesis and biological evaluation of several structural analogs of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand. In: Bioorganic and Medicinal Chemistry. 2007 ; Vol. 15, No. 2. pp. 854-867.
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