dc.contributor.author |
Stevenson, Ralph |
en |
dc.contributor.author |
Azimi, I |
en |
dc.contributor.author |
Flanagan, Jack |
en |
dc.contributor.author |
Inserra, M |
en |
dc.contributor.author |
Vetter, I |
en |
dc.contributor.author |
Monteith, GR |
en |
dc.contributor.author |
Denny, WD |
en |
dc.date.accessioned |
2018-10-22T20:36:16Z |
en |
dc.date.issued |
2018-07-23 |
en |
dc.identifier.citation |
Bioorganic & medicinal chemistry 26(12):3406-3413 Jul 2018 |
en |
dc.identifier.issn |
0968-0896 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/43068 |
en |
dc.description.abstract |
The proteins Orai1 and STIM1 control store-operated Ca2+ entry (SOCE) into cells. SOCE is important for migration, invasion and metastasis of MDA-MB-231 human triple negative breast cancer (TNBC) cells and has been proposed as a target for cancer drug discovery. Two hit compounds from a medium throughput screen, displayed encouraging inhibition of SOCE in MDA-MB-231 cells, as measured by a Fluorescence Imaging Plate Reader (FLIPR) Ca2+ assay. Following NMR spectroscopic analysis of these hits and reassignment of their structures as 5-hydroxy-5-trifluoromethylpyrazolines, a series of analogues was prepared via thermal condensation reactions between substituted acylhydrazones and trifluoromethyl 1,3-dicarbonyl arenes. Structure-activity relationship (SAR) studies showed that small lipophilic substituents at the 2- and 3-positions of the RHS and 2-, 3- and 4-postions of the LHS terminal benzene rings improved activity, resulting in a novel class of potent and selective inhibitors of SOCE. |
en |
dc.publisher |
Elsevier |
en |
dc.relation.ispartofseries |
Bioorganic and 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.rights.uri |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
en |
dc.title |
An SAR study of hydroxy-trifluoromethylpyrazolines as inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader assay |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.bmc.2018.05.012 |
en |
pubs.issue |
12 |
en |
pubs.begin-page |
3406 |
en |
pubs.volume |
26 |
en |
dc.rights.holder |
Copyright: Elsevier |
en |
dc.identifier.pmid |
29776832 |
en |
pubs.end-page |
3413 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
740616 |
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 |
Pharmacology |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1464-3391 |
en |
pubs.record-created-at-source-date |
2018-05-20 |
en |
pubs.dimensions-id |
29776832 |
en |