dc.contributor.author |
Aman, F |
en |
dc.contributor.author |
Hanif, Muhammad |
en |
dc.contributor.author |
Siddiqui, WA |
en |
dc.contributor.author |
Ashraf, A |
en |
dc.contributor.author |
Filak, LK |
en |
dc.contributor.author |
Reynisson, Johannes |
en |
dc.contributor.author |
Soehnel, Tilo |
en |
dc.contributor.author |
Jamieson, Stephen |
en |
dc.contributor.author |
Hartinger, Christian |
en |
dc.date.accessioned |
2017-07-12T23:11:46Z |
en |
dc.date.issued |
2014-10 |
en |
dc.identifier.citation |
Organometallics 33(19):5546-5553 Oct 2014 |
en |
dc.identifier.issn |
0276-7333 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/34201 |
en |
dc.description.abstract |
Oxicams are a versatile family of heterocyclic compounds, and the two representatives meloxicam and piroxicam are widely used drugs for the treatment of a variety of inflammatory and rheumatic diseases in humans. As cancer-associated inflammation is known to occur in carcinogenesis, we aimed to combine compounds carrying bioactive oxicam moieties with ruthenium(arene) fragments, known for anticancer activity. RuII(arene) complexes with methyl ester derivatives of the oxicam scaffold were prepared and characterized by standard methods and crystallographically. The organoruthenium compounds formed from RuII(η6-p-cymene) chlorido moieties and oxicam-based ligands were subjected to bioanalytical investigations to establish their physicochemical properties with regard to stability in DMSO and water as well as reactivity toward the amino acids l-histidine (His), l-methionine (Met), and l-cysteine (Cys) and the DNA model compound guanosine 5′-monophosphate (5′-GMP). The compounds hydrolyzed rapidly in water to give the respective aqua complexes, formed amino acid complexes with Met and His, but decompose with Cys, while interaction with 5′-GMP was through its phosphate residue. The anticancer activity of the complexes against the colon carcinoma HCT116 and breast cancer MDA MB 231 cancer cell lines was established using an in vitro assay. The cytotoxicity was found strongly dependent on the lipophilicity of the compound, as was shown through correlation with log kw and clog P values of the ligands. The most lipophilic compound [chlorido(methyl 4-oxido-2-benzyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide)(η6-p-cymene)ruthenium(II)] was the most active in the cell assays, with an IC50 of 80 μM in HCT116 cells. |
en |
dc.publisher |
American Chemical Society |
en |
dc.relation.ispartofseries |
Organometallics |
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 |
Anticancer Ruthenium(η 6 - p -cymene) Complexes of Nonsteroidal Anti-inflammatory Drug Derivatives |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/om500825h |
en |
pubs.issue |
19 |
en |
pubs.begin-page |
5546 |
en |
pubs.volume |
33 |
en |
dc.rights.holder |
Copyright: American Chemical Society |
en |
pubs.end-page |
5553 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
460499 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
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 |
1520-6041 |
en |
pubs.record-created-at-source-date |
2017-07-13 |
en |