title: (-)-Dibromophakellin: an alpha2B adrenoceptor agonist isolated from the Australian marine sponge, Acanthella costata.
abstract: Bioassay-guided fractionation of the organic extract from the marine sponge Acanthella costata resulted in the isolation of the known natural product, (-)-dibromophakellin (1). Using a fluorescence imaging plate reader (FLIPR) based assay, compound 1 was identified as displaying agonist activity against the alpha(2B) adrenoceptor, with an EC(50) of 4.2muM. Debromination and Suzuki-Miyaura coupling reactions were undertaken in order to provide structure activity data about the pyrrole ring of this marine metabolite. These synthetic studies generated the known natural product analogues, (-)-phakellin (2), and (-)-monobromophakellin (3), along with the new synthetic derivatives (-)-4-bromo-5-phenylphakellin (5) and (-)-4,5-diphenylphakellin (6). Substitution of the C-5 Br of 1 with H (2 and 3) or phenyl (5 and 6) resulted in loss of activity indicating that Br at C-5 is required for agonist activity.
authors.affiliation: Eskitis Institute, Griffith University, Brisbane QLD 4111, Australia.
authors.forename: Rohan A
authors.initials: RA
authors.lastname: Davis
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Fechner
authors.forename: Melissa
authors.initials: M
authors.lastname: Sykes
authors.forename: Agatha
authors.initials: A
authors.lastname: Garavelas
authors.forename: David M
authors.initials: DM
authors.lastname: Pass
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Carroll
authors.forename: Rama
authors.initials: R
authors.lastname: Addepalli
authors.forename: Vicky M
authors.initials: VM
authors.lastname: Avery
authors.forename: John N A
authors.initials: JN
authors.lastname: Hooper
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D001315:Australia; D002460:Cell Line; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D011161:Porifera / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D000316:Adrenergic alpha-Agonists; D006576:Heterocyclic Compounds, 4 or More Rings; C541047:dibromophakellin