Callyspongisines A-D: bromopyrrole alkaloids from an Australian marine sponge, Callyspongia sp.
An extract of the Great Australian Bight marine sponge Callyspongia sp. (CMB-01152) displayed inhibitory activity against the neurodegenerative disease kinase targets casein kinase 1 (CK1), cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3 (GSK3β). Chemical investigation, employing HPLC-DAD-MS single ion extraction protocols, facilitated identification of the new bromopyrrole alkaloids, callyspongisines A-D (1-4), and two known co-metabolites, hymenialdisine (5) and 2-bromoaldisine (6). Structure elucidation of 1-6 was supported by detailed spectroscopic analysis and chemical interconversion, as well as biosynthetic and synthetic considerations. Callyspongisine A (1) is only the second reported example of a natural imino-oxazoline, and the first to feature a spiro heterocyclic framework, while callyspongisines B-D (2-4) were speculated to be storage and handling artefacts of 1. The kinase inhibitory activity detected in Callyspongia sp. (CMB-01152) was attributed to 5.
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia. r.capon@uq.edu.au.
Fabien
F
Plisson
Pritesh
P
Prasad
Xue
X
Xiao
Andrew M
AM
Piggott
Xiao-cong
XC
Huang
Zeinab
Z
Khalil
Robert J
RJ
Capon
D000818:Animals; D001315:Australia; D047128:Callyspongia / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D011494:Protein Kinases