A search for kinase inhibitors and antibacterial agents: bromopyrrolo-2-aminoimidazoles from a deep-water Great Australian Bight sponge, Axinella sp

Biological screening of a deep-water Great Australian Bight marine sponge, Axinella sp., detected inhibition against the neurodegenerative disease kinase targets CDK5/p25, CK1δ, and GSK3β, as well as significant levels of antibacterial activity. Chemical fractionation returned 18 secondary metabolit...

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Published inTetrahedron letters Vol. 53; no. 29; pp. 3784 - 3787
Main Authors Zhang, Hua, Khalil, Zeinab, Conte, Melissa M., Plisson, Fabien, Capon, Robert J.
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier Ltd 18.07.2012
Elsevier
Subjects
Antibacterial
Antiinfectives and antibacterials
Australia
Axinella
Axinella sp
Bromopyrrolo-2-aminoimidazole
Chemistry
Chemistry, Organic
Chlorides
Inhibitors
Kinase inhibitor
Kinases
Marine
Metabolites
Neurodegenerative disease
Physical Sciences
Science & Technology
Searching
Sponges
ISW, Australia, Great Australian Bight
Bromopyrrolo-2-aminoimidazole
Neurodegenerative disease
Antibacterial
Axinella sp
Kinase inhibitor
STYLISSADINE
NATURAL-PRODUCTS
COMPOUND
HYMENIACIDON SP
AGELAS-OROIDES
MARINE SPONGE
MASSADINE
PYRROLE-IMIDAZOLE ALKALOIDS
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Summary:Biological screening of a deep-water Great Australian Bight marine sponge, Axinella sp., detected inhibition against the neurodegenerative disease kinase targets CDK5/p25, CK1δ, and GSK3β, as well as significant levels of antibacterial activity. Chemical fractionation returned 18 secondary metabolites identified by detailed spectroscopic analysis as three new bromopyrrolo-2-aminoimidazoles, 14-O-sulfate massadine (1), 14-O-methyl massadine (2), and 3-O-methyl massadine chloride (3), together with the known metabolites massadine chloride (4), massadine (5), stylissadine B (6), axinellamines A–C (7–9), hymenin (10), stevensine (also known as odiline) (11), tauroacidin A (12), hymenidin (13), taurodispacamide A (14), oroidin (15), debromohymenialdisine (16), hymenialdisine (17), and aldisin (18). Armed with this focused natural product chemical diversity library, we re-established that 16 and 17 were nM kinase inhibitors, and determined that 3, 6, and 12–15 were sub μM antibacterials.
Bibliography:Australian Research Council
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0040-4039
1873-3581
DOI:10.1016/j.tetlet.2012.05.051