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

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• 作者：Hua Zhang^&dagger ; ; Zeinab Khalil ; Melissa M. Conte ; Fabien Plisson ; Robert J. Capon ; ^{r.capon@uq.edu.au}
• 关键词：Axinella sp. ; Bromopyrrolo-2-aminoimidazole ; Neurodegenerative disease ; Kinase inhibitor ; Antibacterial
• 刊名：Tetrahedron Letters
• 出版年：2012
• 出版时间：18 July, 2012
• 年：2012
• 卷：53
• 期：29
• 页码：3784-3787
• 全文大小：534 K

文摘

Biological screening of a deep-water Great Australian Bight marine sponge, Axinella sp., detected inhibition against the neurodegenerative disease kinase targets CDK5/p25, CK1¦Ä, and GSK3¦Â, 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 (g class=""boldFont"">1g>), 14-O-methyl massadine (g class=""boldFont"">2g>), and 3-O-methyl massadine chloride (g class=""boldFont"">3g>), together with the known metabolites massadine chloride (g class=""boldFont"">4g>), massadine (g class=""boldFont"">5g>), stylissadine B (g class=""boldFont"">6g>), axinellamines A-C (g class=""boldFont"">7g>-g class=""boldFont"">9g>), hymenin (g class=""boldFont"">10g>), stevensine (also known as odiline) (g class=""boldFont"">11g>), tauroacidin A (g class=""boldFont"">12g>), hymenidin (g class=""boldFont"">13g>), taurodispacamide A (g class=""boldFont"">14g>), oroidin (g class=""boldFont"">15g>), debromohymenialdisine (g class=""boldFont"">16g>), hymenialdisine (g class=""boldFont"">17g>), and aldisin (g class=""boldFont"">18g>). Armed with this focused natural product chemical diversity library, we re-established that g class=""boldFont"">16g> and g class=""boldFont"">17g> were nM kinase inhibitors, and determined that g class=""boldFont"">3g>, g class=""boldFont"">6g>, and g class=""boldFont"">12g>-g class=""boldFont"">15g> were sub ¦ÌM antibacterials.