dc.contributor.author |
Movassaghi, Sanam |
en |
dc.contributor.author |
Leung, Yee Fun |
en |
dc.contributor.author |
Hanif, Muhammad |
en |
dc.contributor.author |
Lee, Betty |
en |
dc.contributor.author |
Holtkamp, Hannah |
en |
dc.contributor.author |
Tu, Jason KY |
en |
dc.contributor.author |
Soehnel, Tilo |
en |
dc.contributor.author |
Jamieson, Stephen |
en |
dc.contributor.author |
Hartinger, Christian |
en |
dc.date.accessioned |
2020-05-14T04:51:59Z |
en |
dc.date.issued |
2018-07 |
en |
dc.identifier.issn |
0020-1669 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/50699 |
en |
dc.description.abstract |
RuII(η6-arene) compounds carrying bioactive flavonol ligands have shown promising anticancer activity against tumor cells via a multitargeting mode of action, i.e., through interaction with DNA and inhibition of topoisomerase IIα. By introducing a novel arene ligand based on the amino acid l-phenylalanine (Phe), we aimed to alter the pharmacological properties of the complexes. We report here a series of novel RuII(η6-arene)Cl complexes with different substituents on the phenyl ring of the flavonol which should maintain the multitargeting capability of the parent η6- p-cymene (cym) complexes. Studies with selected examples revealed stability in aqueous solution after quickly forming aqua complexes but rapid decomposition in pure DMSO. The reactions with protein and DNA models proceeded quickly and resulted in cleavage of the flavonol or adduct formation, respectively. The compounds were found to be cytotoxic with significant antiproliferative activity in cancer cells with IC50 values in the low μM range, while not following the same trends as observed for the cym analogues. Notably, the cellular accumulation of the new derivatives was significantly higher than for their respective cym complexes, and they induced DNA damage in a manner similar to that of cisplatin but to a lesser extent. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Inorganic 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 |
A Bioactive l-Phenylalanine-Derived Arene in Multitargeted Organoruthenium Compounds: Impact on the Antiproliferative Activity and Mode of Action. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/acs.inorgchem.8b01187 |
en |
pubs.issue |
14 |
en |
pubs.begin-page |
8521 |
en |
pubs.volume |
57 |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.end-page |
8529 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
746795 |
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 |
Chemistry |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1520-510X |
en |
pubs.record-created-at-source-date |
2018-06-28 |
en |
pubs.dimensions-id |
29949354 |
en |