dc.contributor.author |
Pilkington, Lisa |
en |
dc.contributor.author |
Sparrow, Kevin |
en |
dc.contributor.author |
Rees, Shaun |
en |
dc.contributor.author |
Paulin, Emily |
en |
dc.contributor.author |
van Rensburg, Michelle |
en |
dc.contributor.author |
Xu, Chris Sun |
en |
dc.contributor.author |
Langley, Ries |
en |
dc.contributor.author |
Leung, Ka Ho Ivanhoe |
en |
dc.contributor.author |
Reynisson, Jóhannes |
en |
dc.contributor.author |
Leung, Yee Fun |
en |
dc.contributor.author |
Barker, David |
en |
dc.date.accessioned |
2020-05-14T04:26:52Z |
en |
dc.date.issued |
2020-04 |
en |
dc.identifier.issn |
1768-3254 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/50686 |
en |
dc.description.abstract |
Phospholipases are enzymes that are involved in the hydrolysis of acyl and phosphate esters of phospholipids, generating secondary messengers that have implications in various cellular processes including proliferation, differentiation and motility. As such inhibitors of phospholipases have been widely studied for their use as anti-cancer therapeutics. Phosphatidylcholine-specific phospholipase C (PC-PLC) is implicated in the progression of a number of cancer cell lines including aggressing triple-negative breast cancers. Most current studies on PC-PLC have utilised D609 as the standard inhibitor however it is known to have multiple failings, including poor stability in aqueous media. 2-Morpholinobenzoic acids were recently identified using vHTS as a potential class of lead compounds, with improvements over D609. In this work 129 analogues in this class were prepared and their PC-PLC inhibitory activity was assessed. It was found that the majority of these novel compounds had improved activity when compared to D609 with the most potent inhibitors completely inhibiting enzyme activity. It was determined that the best compound/s contained a morpholino and 2-substituted N-benzyl moieties with these findings explained using molecular modelling. The compounds reported here will allow for improved study of PC-PLC activity. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
European journal of medicinal chemistry |
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. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
Development, synthesis and biological investigation of a novel class of potent PC-PLC inhibitors. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.ejmech.2020.112162 |
en |
pubs.begin-page |
112162 |
en |
pubs.volume |
191 |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
795990 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Auckland Cancer Research |
en |
pubs.org-id |
Molecular Medicine |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Chemistry |
en |
dc.identifier.eissn |
1768-3254 |
en |
pubs.record-created-at-source-date |
2020-02-27 |
en |
pubs.dimensions-id |
32101781 |
en |