dc.contributor.author |
Wang, Jiayi |
en |
dc.contributor.author |
Kaiser, M |
en |
dc.contributor.author |
Copp, Brent |
en |
dc.coverage.spatial |
Switzerland |
en |
dc.date.accessioned |
2017-10-17T21:26:54Z |
en |
dc.date.available |
2014-05-04 |
en |
dc.date.issued |
2014-05-28 |
en |
dc.identifier.citation |
Marine Drugs, 12(6):3138-3160, 28 May 2014 |
en |
dc.identifier.issn |
1660-3397 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/36123 |
en |
dc.description.abstract |
Pure compound screening has previously identified the indolglyoxy lamidospermidine ascidian metabolites didemnidine A and B (2 and 3) to be weak growth inhibitors of Trypanosoma brucei rhodesiense (IC50 59 and 44 μM, respectively) and Plasmodium falciparum (K1 dual drug resistant strain) (IC50 41 and 15 μM, respectively), but lacking in selectivity (L6 rat myoblast, IC50 24 μM and 25 μM, respectively). To expand the structure-activity relationship of this compound class towards both parasites, we have prepared and biologically tested a library of analogues that includes indoleglyoxyl and indoleacetic "capping acids", and polyamines including spermine (PA3-4-3) and extended analogues PA3-8-3 and PA3-12-3. 7-Methoxy substituted indoleglyoxylamides were typically found to exhibit the most potent antimalarial activity (IC50 10-92 nM) but with varying degrees of selectivity versus the L6 rat myoblast cell line. A 6-methoxyindolglyoxylamide analogue was the most potent growth inhibitor of T. brucei (IC50 0.18 μM) identified in the study: it, however, also exhibited poor selectivity (L6 IC50 6.0 μM). There was no apparent correlation between antimalarial and anti-T. brucei activity in the series. In vivo evaluation of one analogue against Plasmodium berghei was undertaken, demonstrating a modest 20.9% reduction in parasitaemia. |
en |
dc.description.uri |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071569/ |
en |
dc.language |
English |
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-nc-sa/3.0/ |
en |
dc.subject |
Animals |
en |
dc.subject |
Antimalarials |
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dc.subject |
Cell Line |
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dc.subject |
Female |
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dc.subject |
Inhibitory Concentration 50 |
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dc.subject |
Mice |
en |
dc.subject |
Myoblasts |
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dc.subject |
Parasitic Sensitivity Tests |
en |
dc.subject |
Plasmodium falciparum |
en |
dc.subject |
Polyamines |
en |
dc.subject |
Rats |
en |
dc.subject |
Structure-Activity Relationship |
en |
dc.subject |
Trypanocidal Agents |
en |
dc.subject |
Trypanosoma brucei rhodesiense |
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dc.title |
Investigation of indolglyoxamide and indolacetamide analogues of polyamines as antimalarial and antitrypanosomal agents |
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dc.type |
Journal Article |
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dc.identifier.doi |
10.3390/md12063138 |
en |
pubs.issue |
6 |
en |
pubs.begin-page |
3138 |
en |
pubs.volume |
12 |
en |
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
24879541 |
en |
pubs.author-url |
http://www.mdpi.com/1660-3397/12/6/3138 |
en |
pubs.end-page |
3160 |
en |
pubs.publication-status |
Published online |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
440893 |
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 |
dc.identifier.pii |
md12063138 |
en |
pubs.record-created-at-source-date |
2017-10-18 |
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pubs.dimensions-id |
24879541 |
en |