dc.contributor.author |
Lin, ZG |
en |
dc.contributor.author |
Murray, PM |
en |
dc.contributor.author |
Ding, YY |
en |
dc.contributor.author |
Denny, William |
en |
dc.contributor.author |
Ferguson, Lynnette |
en |
dc.date.accessioned |
2011-11-17T17:24:58Z |
en |
dc.date.issued |
2010-08-07 |
en |
dc.identifier.citation |
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis 690(1-2):81-88 07 Aug 2010 |
en |
dc.identifier.issn |
0027-5107 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/9260 |
en |
dc.description.abstract |
Histone deacetylase (HDAC) inhibitors regulate many biological responses, including anti-inflammatory and anti-cancer effects. We sought to identify novel classes of HDAC inhibitors from in-house compound libraries. Initially, compounds from 26 different structural classes that showed anti-inflammatory effects in a pre-screen in HEK293T cells were tested in vitro for HDAC inhibition, using a commercial fluorescence assay. The known HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) were used as positive controls. Examples of three different structural classes (anilinoacridines, phenylpyrrolocarbazoles and benzofurylquinazolines) showed significant inhibition in the HDAC assay, and small subsets of these were also evaluated, seeking initial structure–activity relationships (SAR) for each class. Several of the most effective compounds from this HDAC screen were evaluated for their effects on the expression of the pro-inflammatory gene, IL1-α, and the cancer-related genes, p53, p21, E-cadherin and C-MYC. While the benzofurylquinazolines increased the expression level of the pro-inflammatory gene IL1-α as well as p21 and p53 in the PC3 cell line, a phenylpyrrolocarbazole had the converse effect on p53 expression. Several of the compounds showed in vitro HDAC inhibition ability in PC3, HCT116 and NIH-3T3 cell lines comparable to that of SAHA. |
en |
dc.language |
EN |
en |
dc.publisher |
Elsevier B.V. |
en |
dc.relation.ispartofseries |
Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis |
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://www.sherpa.ac.uk/romeo/issn/0027-5107/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Epigenetics |
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dc.subject |
Histone deacetylase inhibitor |
en |
dc.subject |
Chronic inflammation |
en |
dc.subject |
Quinazolines |
en |
dc.subject |
NF-KAPPA-B |
en |
dc.subject |
SUBEROYLANILIDE HYDROXAMIC ACID |
en |
dc.subject |
GENE-EXPRESSION |
en |
dc.subject |
EPIGENETIC REGULATION |
en |
dc.subject |
CANCER-TREATMENT |
en |
dc.subject |
CELL-GROWTH |
en |
dc.subject |
DIFFERENTIATION |
en |
dc.subject |
P53 |
en |
dc.subject |
TRICHOSTATIN |
en |
dc.subject |
ACETYLATION |
en |
dc.title |
Quinazolines as novel anti-inflammatory histone deacetylase inhibitors |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.mrfmmm.2010.06.007 |
en |
pubs.issue |
1-2 |
en |
pubs.begin-page |
81 |
en |
pubs.volume |
690 |
en |
dc.rights.holder |
Copyright: ELSEVIER BV |
en |
dc.identifier.pmid |
20558185 |
en |
pubs.end-page |
88 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
120205 |
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 |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2011-11-17 |
en |
pubs.dimensions-id |
20558185 |
en |