title: Desulfohaplosamate, a new phosphate-containing steroid from Dasychalina sp., is a selective cannabinoid CB2 receptor ligand.
abstract: 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 CB(1) and CB(2) receptors through a binding test. Desulfohaplosamate (2) showed a selective affinity for CB(2) receptors in the low μM 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.
authors.affiliation: Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Chianese
authors.forename: Ernesto
authors.initials: E
authors.lastname: Fattorusso
authors.forename: Orazio
authors.initials: O
authors.lastname: Taglialatela-Scafati
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bavestrello
authors.forename: Barbara
authors.initials: B
authors.lastname: Calcinai
authors.forename: Henny A
authors.initials: HA
authors.lastname: Dien
authors.forename: Alessia
authors.initials: A
authors.lastname: Ligresti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000818:Animals; D015394:Molecular Structure; D010710:Phosphates / Q000737:chemistry*; D011161:Porifera / Q000737:chemistry*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D013256:Steroids / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010710:Phosphates; D043885:Receptor, Cannabinoid, CB2; D013256:Steroids