dc.contributor.author |
Harper, Jacquie |
en |
dc.contributor.author |
Khalil, Iman |
en |
dc.contributor.author |
Shaw, L |
en |
dc.contributor.author |
Bourguet-Kondracki, M-L |
en |
dc.contributor.author |
Dubois, J |
en |
dc.contributor.author |
Valentin, A |
en |
dc.contributor.author |
Barker, David |
en |
dc.contributor.author |
Copp, Brent |
en |
dc.date.accessioned |
2017-10-15T22:42:09Z |
en |
dc.date.available |
2015-08-04 |
en |
dc.date.issued |
2015-08-10 |
en |
dc.identifier.citation |
Marine Drugs, 13(8):5102-5110, 10 Aug 2015 |
en |
dc.identifier.issn |
1660-3397 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/36055 |
en |
dc.description.abstract |
In an effort to more accurately define the mechanism of cell death and to establish structure-activity relationship requirements for the marine meroterpenoid alkaloids thiaplidiaquinones A and B, we have evaluated not only the natural products but also dioxothiazine regioisomers and two precursor quinones in a range of bioassays. While the natural products were found to be weak inducers of ROS in Jurkat cells, the dioxothiazine regioisomer of thiaplidiaquinone A and a synthetic precursor to thiaplidiaquinone B were found to be moderately potent inducers. Intriguingly, and in contrast to previous reports, the mechanism of Jurkat cell death (necrosis vs. apoptosis) was found to be dependent upon the positioning of one of the geranyl sidechains in the compounds with thiaplidiaquinone A and its dioxothiazine regioisomer causing death dominantly by necrosis, while thiaplidiaquinone B and its dioxothiazine isomer caused cell death via apoptosis. The dioxothiazine regioisomer of thiaplidiaquinone A exhibited more potent in vitro antiproliferative activity against human tumor cells, with NCI sub-panel selectivity towards melanoma cell lines. The non-natural dioxothiazine regioisomers were also more active in antiplasmodial and anti-farnesyltransferase assays than their natural product counterparts. The results highlight the important role that natural product total synthesis can play in not only helping understand the structural basis of biological activity of natural products, but also the discovery of new bioactive scaffolds. |
en |
dc.description.uri |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557015/ |
en |
dc.format.medium |
Electronic |
en |
dc.language |
English |
en |
dc.publisher |
MDPI |
en |
dc.relation.ispartofseries |
Marine Drugs |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://sherpa.ac.uk/romeo/issn/1660-3397/
http://www.mdpi.com/about/openaccess |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
en |
dc.subject |
Cell Line, Tumor |
en |
dc.subject |
Jurkat Cells |
en |
dc.subject |
Humans |
en |
dc.subject |
Terpenes |
en |
dc.subject |
Quinones |
en |
dc.subject |
Biological Products |
en |
dc.subject |
Apoptosis |
en |
dc.subject |
Cell Proliferation |
en |
dc.subject |
Structure-Activity Relationship |
en |
dc.subject |
Aquatic Organisms |
en |
dc.title |
Structure-Activity Relationships of the Bioactive Thiazinoquinone Marine Natural Products Thiaplidiaquinones A and B |
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dc.type |
Journal Article |
en |
dc.identifier.doi |
10.3390/md13085102 |
en |
pubs.issue |
8 |
en |
pubs.begin-page |
5102 |
en |
pubs.volume |
13 |
en |
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
26266415 |
en |
pubs.author-url |
http://www.mdpi.com/1660-3397/13/8/5102 |
en |
pubs.end-page |
5110 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
495097 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Chemistry |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1660-3397 |
en |
pubs.record-created-at-source-date |
2017-10-16 |
en |
pubs.dimensions-id |
26266415 |
en |