(-)-Dibromophakellin: an alpha2B adrenoceptor agonist isolated from the Australian marine sponge, Acanthella costata.
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.
Davis
Rohan A
RA
Eskitis Institute, Griffith University, Brisbane QLD 4111, Australia.
Fechner
Gregory A
GA
Sykes
Melissa
M
Garavelas
Agatha
A
Pass
David M
DM
Carroll
Anthony R
AR
Addepalli
Rama
R
Avery
Vicky M
VM
Hooper
John N A
JN
Quinn
Ronald J
RJ
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
D000316:Adrenergic alpha-Agonists; D006576:Heterocyclic Compounds, 4 or More Rings; C541047:dibromophakellin