dc.contributor.author |
Łomzik, Michał |
|
dc.contributor.author |
Hanif, Muhammad |
|
dc.contributor.author |
Budniok, Aleksandra |
|
dc.contributor.author |
Błauż, Andrzej |
|
dc.contributor.author |
Makal, Anna |
|
dc.contributor.author |
Tchoń, Daniel M |
|
dc.contributor.author |
Leśniewska, Barbara |
|
dc.contributor.author |
Tong, Kelvin KH |
|
dc.contributor.author |
Movassaghi, Sanam |
|
dc.contributor.author |
Söhnel, Tilo |
|
dc.contributor.author |
Jamieson, Stephen MF |
|
dc.contributor.author |
Zafar, Ayesha |
|
dc.contributor.author |
Reynisson, Jóhannes |
|
dc.contributor.author |
Rychlik, Błażej |
|
dc.contributor.author |
Hartinger, Christian G |
|
dc.contributor.author |
Plażuk, Damian |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2024-06-05T02:12:33Z |
|
dc.date.available |
2024-06-05T02:12:33Z |
|
dc.date.issued |
2020-10 |
|
dc.identifier.citation |
(2020). Inorganic Chemistry, 59(20), 14879-14890. |
|
dc.identifier.issn |
0020-1669 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/68569 |
|
dc.description.abstract |
Ispinesib is a potent inhibitor of kinesin spindle protein (KSP), which has been identified as a promising target for antimitotic anticancer drugs. Herein, we report the synthesis of half-sandwich complexes of Ru, Os, Rh, and Ir bearing the ispinesib-derived <i>N</i>,<i>N</i>-bidentate ligands (<i>R</i>)- and (<i>S</i>)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one and studies on their chemical and biological properties. Using the enantiomerically pure (<i>R</i>)- and (<i>S</i>)-forms of the ligand, depending on the organometallic moiety, either the <i>S</i><sub>M</sub>,<i>R</i> or <i>R</i><sub>M</sub>,<i>S</i> diastereomers, respectively, were observed in the molecular structures of the Ru- and Os(cym) (cym = η<sup>6</sup>-<i>p</i>-cymene) compounds, whereas the <i>R</i><sub>M</sub>,<i>R</i> or <i>S</i><sub>M</sub>,<i>S</i> diastereomers were found for the Rh- and Ir(Cp*) (Cp* = η<sup>5</sup>-pentamethylcyclopentadienyl) derivatives. However, density functional theory (DFT) calculations suggest that the energy difference between the diastereomers is very small, and therefore a mixture of both will be present in solution. The organometallics exhibited varying antiproliferative activity in a series of human cancer cell lines, with the complexes featuring the (<i>R</i>)-enantiomer of the ligand being more potent than the (<i>S</i>)-configured counterparts. Notably, the Rh and Ir complexes demonstrated high KSP inhibitory activity, even at 1 nM concentration, which was independent of the chirality of the ligand, whereas the Ru and especially the Os derivatives were much less active. |
|
dc.format.medium |
Print-Electronic |
|
dc.language |
eng |
|
dc.publisher |
American Chemical Society (ACS) |
|
dc.relation.ispartofseries |
Inorganic chemistry |
|
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. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Cell Line, Tumor |
|
dc.subject |
Humans |
|
dc.subject |
Metals, Heavy |
|
dc.subject |
Benzamides |
|
dc.subject |
Quinazolines |
|
dc.subject |
Antineoplastic Agents |
|
dc.subject |
Antioxidants |
|
dc.subject |
Ligands |
|
dc.subject |
Drug Screening Assays, Antitumor |
|
dc.subject |
Cell Proliferation |
|
dc.subject |
Protein Binding |
|
dc.subject |
Stereoisomerism |
|
dc.subject |
Coordination Complexes |
|
dc.subject |
Molecular Docking Simulation |
|
dc.subject |
Kinesins |
|
dc.subject |
3402 Inorganic Chemistry |
|
dc.subject |
34 Chemical Sciences |
|
dc.subject |
Cancer |
|
dc.subject |
Science & Technology |
|
dc.subject |
Physical Sciences |
|
dc.subject |
Chemistry, Inorganic & Nuclear |
|
dc.subject |
Chemistry |
|
dc.subject |
RUTHENIUM COMPLEXES |
|
dc.subject |
ANTICANCER AGENTS |
|
dc.subject |
CRYSTAL-STRUCTURE |
|
dc.subject |
DERIVATIVES |
|
dc.subject |
PACLITAXEL |
|
dc.subject |
TAXANES |
|
dc.subject |
PYRIMIDINE |
|
dc.subject |
COLCHICINE |
|
dc.subject |
ANALOGS |
|
dc.subject |
0302 Inorganic Chemistry |
|
dc.subject |
0306 Physical Chemistry (incl. Structural) |
|
dc.subject |
0399 Other Chemical Sciences |
|
dc.subject |
3403 Macromolecular and materials chemistry |
|
dc.title |
Metal-Dependent Cytotoxic and Kinesin Spindle Protein Inhibitory Activity of Ru, Os, Rh, and Ir Half-Sandwich Complexes of Ispinesib-Derived Ligands |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1021/acs.inorgchem.0c00957 |
|
pubs.issue |
20 |
|
pubs.begin-page |
14879 |
|
pubs.volume |
59 |
|
dc.date.updated |
2024-05-03T21:32:42Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
33003697 (pubmed) |
|
pubs.author-url |
https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c00957 |
|
pubs.end-page |
14890 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
820592 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Science |
|
pubs.org-id |
Chemistry |
|
pubs.org-id |
Science Research |
|
pubs.org-id |
Medical Sciences |
|
pubs.org-id |
Pharmacology |
|
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
|
dc.identifier.eissn |
1520-510X |
|
pubs.record-created-at-source-date |
2024-05-04 |
|
pubs.online-publication-date |
2020-10 |
|