Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp.
Abstract Screening a library of Southern Australian and Antarctic marine invertebrates and algae for inhibitors of neurodegenerative disease kinase targets casein kinase 1 (CK1δ), cyclin‐dependent kinase 5 (CDK5) and glycogen synthase kinase 3β (GSK3β) identified a Western Australian Didemnum specie...
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crwiley:10.1002/cmdc.201200169 2024-09-15T17:42:24+00:00 Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp. Plisson, Fabien Conte, Melissa Khalil, Zeinab Huang, Xiao‐Cong Piggott, Andrew M. Capon, Robert J. 2012 http://dx.doi.org/10.1002/cmdc.201200169 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcmdc.201200169 http://onlinelibrary.wiley.com/wol1/doi/10.1002/cmdc.201200169/fullpdf en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor ChemMedChem volume 7, issue 6, page 983-990 ISSN 1860-7179 1860-7187 journal-article 2012 crwiley https://doi.org/10.1002/cmdc.201200169 2024-08-27T04:28:07Z Abstract Screening a library of Southern Australian and Antarctic marine invertebrates and algae for inhibitors of neurodegenerative disease kinase targets casein kinase 1 (CK1δ), cyclin‐dependent kinase 5 (CDK5) and glycogen synthase kinase 3β (GSK3β) identified a Western Australian Didemnum species (CMB‐02127) as a high‐priority specimen. Chemical fractionation returned the known aromatic alkaloids ningalins B–D as the major metabolites, together with six minor metabolites, the new ningalins E–G and the known hexacyclic pyrrole alkaloids lamellarins Z, G and A6. All structures were assigned by detailed spectroscopic analysis and literature comparisons, and the structural assignments were supported by biosynthetic considerations. The ningalins showed potent and broad inhibition across the three kinases, while the lamellarins were generally more selective for CDK5. Docking studies using published X‐ray crystal structures of CDK5 revealed both scaffolds target the ATP binding pocket. Article in Journal/Newspaper Antarc* Antarctic Wiley Online Library ChemMedChem 7 6 983 990 |
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Open Polar |
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Wiley Online Library |
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crwiley |
language |
English |
description |
Abstract Screening a library of Southern Australian and Antarctic marine invertebrates and algae for inhibitors of neurodegenerative disease kinase targets casein kinase 1 (CK1δ), cyclin‐dependent kinase 5 (CDK5) and glycogen synthase kinase 3β (GSK3β) identified a Western Australian Didemnum species (CMB‐02127) as a high‐priority specimen. Chemical fractionation returned the known aromatic alkaloids ningalins B–D as the major metabolites, together with six minor metabolites, the new ningalins E–G and the known hexacyclic pyrrole alkaloids lamellarins Z, G and A6. All structures were assigned by detailed spectroscopic analysis and literature comparisons, and the structural assignments were supported by biosynthetic considerations. The ningalins showed potent and broad inhibition across the three kinases, while the lamellarins were generally more selective for CDK5. Docking studies using published X‐ray crystal structures of CDK5 revealed both scaffolds target the ATP binding pocket. |
format |
Article in Journal/Newspaper |
author |
Plisson, Fabien Conte, Melissa Khalil, Zeinab Huang, Xiao‐Cong Piggott, Andrew M. Capon, Robert J. |
spellingShingle |
Plisson, Fabien Conte, Melissa Khalil, Zeinab Huang, Xiao‐Cong Piggott, Andrew M. Capon, Robert J. Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp. |
author_facet |
Plisson, Fabien Conte, Melissa Khalil, Zeinab Huang, Xiao‐Cong Piggott, Andrew M. Capon, Robert J. |
author_sort |
Plisson, Fabien |
title |
Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp. |
title_short |
Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp. |
title_full |
Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp. |
title_fullStr |
Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp. |
title_full_unstemmed |
Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp. |
title_sort |
kinase inhibitor scaffolds against neurodegenerative diseases from a southern australian ascidian, didemnum sp. |
publisher |
Wiley |
publishDate |
2012 |
url |
http://dx.doi.org/10.1002/cmdc.201200169 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcmdc.201200169 http://onlinelibrary.wiley.com/wol1/doi/10.1002/cmdc.201200169/fullpdf |
genre |
Antarc* Antarctic |
genre_facet |
Antarc* Antarctic |
op_source |
ChemMedChem volume 7, issue 6, page 983-990 ISSN 1860-7179 1860-7187 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/cmdc.201200169 |
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ChemMedChem |
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7 |
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6 |
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983 |
op_container_end_page |
990 |
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1810488963073310720 |