Desulfohaplosamate, a new phosphate-containing steroid from Dasychalina sp., is a selective cannabinoid CB2 receptor ligand

• Published in: Steroids Vol. 76; no. 10-11; pp. 998 - 1002
• Main Authors: Chianese, Giuseppina, Fattorusso, Ernesto, Taglialatela-Scafati, Orazio, Bavestrello, Giorgio, Calcinai, Barbara, Dien, Henny A., Ligresti, Alessia, Di Marzo, Vincenzo
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier 01.09.2011
• Subjects: Animals; Biochemistry & Molecular Biology; Biological and medical sciences; cannabinoids; Endocrinology & Metabolism; Fundamental and applied biological sciences. Psychology; Life Sciences & Biomedicine; Medical sciences; Molecular Structure; Neuropharmacology; nuclear magnetic resonance spectroscopy; Pharmacology. Drug treatments; Phosphates - chemistry; Porifera - chemistry; Psychodysleptics: hallucinogen; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptor, Cannabinoid, CB2 - agonists; receptors; Science & Technology; steroids; Steroids - chemistry; Steroids - pharmacology; Structure-Activity Relationship; Vertebrates: endocrinology; Phosphated steroids; CB2 agonist; Sponges; Haplosamate; EXPRESSION; BRAIN; Cannabinoid receptors; Phosphates; Steroid; Agonist; Ligand; Cannabinoid receptor; CB2 cannabinoid receptor; CB
• ISSN: 0039-128X; 1878-5867; 1878-5867
• DOI: 10.1016/j.steroids.2011.03.013

From the polar organic extract of the Indonesian sponge Dasychalina sp. we have isolated haplosamate A (1), a unique C-28 sterol containing a sulfate group at C-3 and a methyl phosphate at C-15, along with its new desulfo analogue 2, whose structure has been secured by detailed NMR investigation. Compounds 1 and 2, as well as their semi-synthetic analogues 3-5, have been evaluated for interaction with CB1 and CB2 receptors through a binding test. Desulfohaplosamate (2) showed a selective affinity for CB2 receptors in the low mu M range, while a semi-synthetic derivative with cleaved ring B showed a complete loss of affinity for both receptors, highlighting the importance of an intact steroid nucleus. To our knowledge, haplosamate derivatives represent the first CB receptor ligands belonging to the class of steroids. (C) 2011 Elsevier Inc. All rights reserved.